AS211 Endocrinology Lecture Notes1

8/3/2019 AS211 Endocrinology Lecture Notes1

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Endocrinology

Endocrinology is the study of hormones in terms of:

Physiological roles (function);

Cellular sources;

Biosynthesis;

Chemistry, storage and metabolism;

Factors and mechanisms controlling hormone secretion;

Cellular mechanisms of hormone action; and,

Pathophysiology of endocrine system dysfunction.

Hormones belong to a class of chemical messengers

that are involved in integration of developmental

events and coordination of physiological processes

Endocrine glands release hormones into the

immediate extracellular space ; the hormones then

enter the circulatory system where they elicit

responses in remote places

1AS211 Endocrinology Notes


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Homeostasis

Homeostasis is the maintenance of a constant internal

environment in the face of a changing externalenvironment

Please note that this definition is relationalin that you

have to mention both the internal and external

environments

Homeostasis has four critical elements:

Sensors which detect changes in the internal (or

external) environment;

A communication network that relays information from

one site to the other;

A central integration and control system that defines

set-points, measures the magnitude of deviations from

the norm and issues out corrective signals; and,

Effectors that carry out the instructions from the central

control system.

Why homeostasis?

Cells of the body require specific conditions to function

AS211 Endocrinology Notes 2


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Homeostasis

How?

Homeostasis is achieved through feedback (negative

but sometimes positive) systems

The example below illustrates a negative feedback

loop where an endocrine tissue releases a hormone

which upregulates a target tissue, the product of the

target tissue downregulates the endocrine tissue

Hormone

Targettissue (+)

Hormone

Endocrinetissue (-)



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Homeostasis

Eg Ca2+ homeostasis


Parafollicular cells Calcitonin

Parathormone

Bone calcium

Parathyroid gland

Dietary intake

Kidney/intestinal

loss

(Increased)

(Decreased)

Blood calcium

Mobilises

Stores


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Hormoneclassification


Hormones

Fatty acid

derivatives-

Eicosanoids

Prostaglandins

ProstacyclinsThromboxanes

Leukotrienes

Amino acid derivatives

TyrosineT3 & T4Catecholamines

(dopamine,

norepinephrine,

epinephrine )

Tryptophan

Serotonin

Melatonin

Glutamic acid

Histamine

Proteins and

peptides Insulin

TRH etc

Steroids

Corticosteroids Gonadal steroids

Androgens

(masculinising)

testosterone

Oestrogens

(feminising)

Oestradiol

Progesterone

Oestrone

Progestins

(progestagens)

Progesterone

Glucocorticoids

(Carbohydrate

metabolism)

Cortisol

Cortisone

Corticosterone

Mineralocorticoids

(Electrolyte balance)

Aldosterone


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Hormoneclassification Peptide and protein hormones

Range in size from 3 AA (thyrotropin releasinghormone) residues to complex proteins(gonadotropins)

Linear chain e.g. angiotensin II

May contain a ring structure e.g. ocytocin andvasopressin

May have two chains linked by disulphide bridgese.g. insulin, thyrotropin (TSH) and the gonadotropins(LH and FSH)

Inter- and intra-chain disulphide bridges may beimportant in defining conformation and functionality

May be glycoproteins e.g. gonadotropins

Some AA residues maybe modified

posttranslationally through amidation, acetylation,cyclisation or sulfation

Some derived from a prohormone which is cleavedto produce the functional form while others comefrom more complex preprohormones throughmultiple cleavages

Regulated secretion synthesised-stored released

Constitutive secretion synthesised and released

Half life is usually a few minutes



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Hormoneclassification Amino acid derivatives

Tyrosine derivatives T3 and T4 (Long half-life typically days) Catecholamines (short half life minutes)

Tryptophan derivatives Melatonin and serotonin

Glutamic acid derivatives Histamines

Steroid hormones Derived from cholesterol

Rate limiting step is conversion of cholesterol topregnenolone

Synthesised in steroidogenic tissues of the adrenalcortex (corticosteroids) and the gonads (gonadalsteroids)

Some synthesised in multiple locations e.g. VitaminD3

Long half life

Eicosanoids

Long chain unsaturated fatty acid derivatives Prostaglandins, prostacyclins, thromboxanes and

leukotrienes

Short half-life - seconds



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Hormonedelivery


Endocrine

Paracrine

Autocrine

Neuroendocrine

Neurocrine

Blood vessel

Blood vessel


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Generalmechanismsofaction

Two major mechanisms 1st messenger 2nd messenger model of

hormone action The hormone (1st messenger) interacts with a

receptor on cell membrane eliciting release ofa 2nd messenger on the cytoplasmic side

The 2nd

messenger is usual a cyclic nucleotidesuch as cyclic adenosine monophosphate(cAMP) or cyclic guanosine monophosphate(cGMP).

E.g. the protein hormones

Action relatively short-lived

Other first messengers interact with anintracellular receptor and alter geneexpression and protein synthesis

E.g. steroid hormones

Action more sustained

There are some hormones that use both

mechanisms or their modifications Hormone receptors serve a recognition

function which is converted into an actionfunction



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Hormone receptors Hormones regulate specific tissues

Receptors provide specificity for hormone-cellinteraction

Receptors can be components of the cellmembrane or may be cytosolic or nuclearelements

Some hormones that are similar in structure

may show (weak) overlap in action e.goxytocin and vasopressin

Others stimulate many tissues e.g. insulin

The implications are that action at individual

tissues should be complemntary For example parathormone action leads to

mobilisation of Ca2+ from bone, increaseduptake from the gut and reduced urinarylosses


Oxytocin Vasopressin

Uterine smooth

muscle contraction

Renal tubular

cAMP production


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Extracellular hormone receptors

Hormones interact with receptor leading to signaltransduction to cytoplasmic side of the membrane

leading to activation of enzymes Most receptors are glycoproteins

Receptor numbers Dynamic, change with cell cycle or state of cellular

differentiation

Depend on developmental or differentiation state

Hormones may regulate the number of their ownreceptors (homospecific) or receptors for otherhormones (heterospecific)

E.g. prolactin up-regulates prolactin receptors in the liverand other tissues

Continued exposure to insulin down-regulates receptorsin lymphocytes

Some responses depend on cell type e.g. receptors forangiotensin II

TRH leads to release of TSH which in turn leads torelease of T3 and T4, the two thyroid hormones downregulate receptors for TRH in pituitary thyrotrophs

Glucocorticoids increase TRH receptors

Changes in receptor numbers prevents overstimulationof target tissues and

Provide a mechanism by which hormones act insequence to modify response from other hormones e.g.FSH and LH act in a sequential manner LH receptorsinduced by FSH



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Receptor cooperativity and

hormone action There are two events that govern the

rate and magnitude of response

Hormone binding and the coupling

between the binding event and the firstbiochemical signal elicited

The binding event can be:

Non-cooperative

Positively cooperative where initial

binding of hormone to receptor increasesaffinity of other receptors to the hormone

Negatively cooperative where the initialbinding of hormone to receptor reducesaffinity of other receptors to the hormonethereby desensitising cells to abnormalconcentration of hormone

Affinity of insulin receptors decreases asoccupancy increases



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Spare receptors Maximal biological response is

achieved when a small percentage ofreceptors are occupied, this increasessensitivity to low concentrations of

circulating hormones Separate receptors for hormone

action

Glucagon and epinephrine stimulate

glycogenolysis and release of glucoseby the liver using separate and distinctreceptors

Both receptors activate hepaticadenylate cyclase

The hormones are released underdifferent physiological circumstancesand their action is non-additive



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Receptor structure

There are four classes of receptors Receptors that are also enzymes e.g. tyrosine

protein kinases or guanylate cyclase

Receptor channels

Receptors that coupled to G (GTP-binding)proteins

Receptors with unknown transductionmechanisms

G protein coupled receptors are the mostcommon

Contain recognition site for ligand (hormone)and site for specific G protein

Receptors made up of single peptide (400-600AA residues)

The N-terminus is extracellular and containssites for N-linked glycosylation

The C-terminus is intracellular and has sites forphosphorylation by protein kinase

The two termini are separated by 7 stretchesof 22-28 hydrophobic conserved residuesseparated by hydrophilic segments amultipass integral membrane protein



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2nd messengers

2nd messengers are the ones that effect a

physiological response The most common are cyclic nucleotides such

as cyclic adenosine monophosphate (cAMP)or guanosine monophosphate (cGMP) whoseformation is catalysed by adenylate cyclaseand guanylate cyclase , respectively

Enzyme cleavage of cyclic ring leads toinactive 5AMP or 5GMP

Each cyclic nucleotide combines with aspecific cyclic nucleotide-dependent proteinkinase

The cAMP-dependent protein kinase is

composed of a catalytic unit and a regulatoryunit

Interaction with cAMP leads to release of anactive catalytic unit

Cyclic nucleotides are rapidly metabolised(phosphodiesterases cleave cyclic bonds),while phosphoprotein phosphatasesdephosphorylate proteins so that conditionsreturn to basal level

In some instances action of cAMP may begenomic through interaction with a cAMPresponsive element binding protein (CREB)



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Receptor signal transduction

Activation of adenylate cyclase is immediate

The receptor and the enzyme may be coupledwith the binding event leading to conformationalchanges e.g. guanylate cyclase

Or receptors may only gain affinity to the enzymeafter binding

Signal transduction may involve monovalent and

divalent cations as well as prostaglandin synthesis One or more regulatory proteins may be part of

the transduction pathway e.g. guanylylnucleotide regulatory protein that exhibitsGTPase activity

G proteins act as transducers Couple membrane bound receptors to effectors

They are heterotrimers that dissociate to liberate anucleotide bound -subunit and a couplex of -and - subunits

Receptor-G protein interaction may result indirect activation of membrane ion channels

(depolarisation or hyperpolarisation leads toresponse)

Other messengers include phosphoinositides,arachidonic acid, inositol triphosphate, diacylglycerol



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Mechanism of action protein

hormones


utside (N-terminus)

side (C- terminus)

Hormone

Receptor

Cell membrane

Inactive G-protein (, , , subunits)

Inactive adenylate cyclase

1

GTP

2

Hormone binds to receptor

Hormone-receptor

complex activates G-

protein increasing

affinity of-subunit to

GTP


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GTP

3

Mechanism of action protein

hormones

Active adenylate cyclase

ATPcAMP+Catalytic unit

Regulatory unit

Inactive cAMP dependentprotein kinase

cAMP

Regulatory unitCatalytic unit+ Active cAMP-dPK

ProteinProtein-PO43-

Cellular response

Enzyme activation

Muscle relaxation

Nerve stimulation

Hormone secretion

etc


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Multiple 2nd messengers


PLC

PIP2

DG

PKC

Ca2+

Ca2+

IP3

ER

Ca2+

Cellular

response

Hormone

Receptor

G protein

Key:PIP2 Phosphoinositol

PLC Phospholipase

DG Diacylglycerol

IP3 Inositol triphosphate

PKC Protein kinase C

ER Endoplasmic reticulum


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Mechanism of action - eicosanoids

Prostaglandins sometimes act as second

messengers or as hormones in their ownright

They are produced in the cell membranemainly from arachidonic acid via the actionof phospholipase A2 (PLA2)

Arachidonic acid formed from linolenic acidthrough elongation and desaturation inresponse to hormones and other stimuli

Arachidonic acid is then converted tounstable endoperoxide intermediatesthrough the cyclooxygenase system

Tissue specific enzymes then convert theintermediates into prostaglandin E2 (PGE2),PGF2, prostacylcin I2 or thromboxane A2

In other tissues arachidonic acid isconverted to leukotrienes (action of 5-lipoxygenase)

PGE2 and PCI2 stimulate adenylate cyclasewhile the mechanism of PGF2 is not clear



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Mechanism of action - eicosanoids


IntracellularExtracellular Cell membrane

Extrinsic

stimuli

(hormones,

hypoxia, pH)

Inactive

phospholipase

Active

phospholipase

Phospholipids

Arachidonic acid

Eicosanoid

hormones

Nucleotide

cyclases

Cyclic

nucleotides

Cellular

response

Humoral

hormones

Target cell

Cellular

response

Nucleotide

cyclases

Cyclic

nucleotides


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Cytosolic hormone receptors Steroid and thyroid hormones attach to

intracellular hormone receptors proteins in

nature Mechanism by which they cross cell membrane is

unknown simple diffusion?

The steroid-receptor complex migrates to thenucleus where it interacts with specificchromosomal protein and DNA

There is evidence that steroid hormones mayreach the nucleus and attach to unoccupiedreceptors within

Binding of receptor-hormone complex tochromatin leads to derepression of specific DNAsequences and increased mRNA synthesis

Each steroid has a specific receptor The receptors belong to a superfamily of zinc

finger proteins

The receptors are dimers; receptor complexed tonon-steroid binding heat shock protein

Receptors bind ligands with high affinity andspecificity

After binding specific ligand, the ligand-inducedtranscription factors influence gene-expressionvia specific DNA elements called hormone-responsive elements



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Mechanism of action -steroids


eroid hormone

Nucleus

Cytoplasm

Receptor

Receptor-

hormone

complex

Complex binds

chromatinleading to

transcription of

mRNA

Ribosomes

translate

new mRNA

into protein

Cellular

response


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Permissive action of hormones

Permissive action is a situation where a hormone must be

there for another hormone to exert its effects usually an

action of steroid and thyroid hormones

This happens through increasing receptors for the second

hormone or modulating the amount of cyclic nucleotide

dependent protein kinase thereby influencing response to

hormones that act on the plasmalemma

The steroid or thyroid hormone may increase synthesis of an

inhibitor of another protein e.g. phosphoprotein

phosphatase whose action antagonises cyclic nucelotide

action

Synergism on the other hand is a physiological response of a

tissue to a combination of two hormones that greatly

exceeds the sum of the individual hormones e.g. FSH has no

detectable effect on enzyme activity of testicular interstitial

cells and LH minimally stimulates such activity. In the

presence of FSH the action of LH is greatly enhanced



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R

AC

Protein hormone

cAMP

Protein

kinase

Protein

substrate

Cellular

response

Membrane

receptors

Protein

synthesis

Calmodulin

Ca2+

Steroid

receptors (R)

DNA

teroid hormone(S)

[S-R]

S+R

mRNA

Permissive action of hormones

Cell membrane

Nucleus


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Stimulus-response coupling

Membrane-mediated hormone action involves

changes in transmembrane potential

A cell is usually 60 90 mV negative on the inside

which makes it electrically excitable

It can be depolarised or hyperpolarised upon

being stimulated

Examples are stimulus-contraction and stimulus-

secretion coupling Role of Ca2+

Modulates adenylate cyclase and cyclic nucleotide

diphosphoesterase activity

Interacts with calcium dependent regulatory

protein called calmodulin Calmodulin (CAM) is a 148 AA stringently

conserved protein with Lsy115 being

trimethylated postranscriptionally, it has 4 Ca2+

binding sites with a high degree of homology (1-3;

2-4) Binding of Ca2+ leads to conformational changes

Only three sites required

Role of CAM Regulate intracellular Ca2+, activate enzymes,

control cellular filamentous organelle activity



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Termination of hormone action

Hormones that act on the plasmalemma are

degraded in the blood by serum enzymes

Decreased stimulation leads to lower production

of cyclic nucelotide

In the absence of further cyclic nucleotide

production residual cyclic nucleotides destroyed

by phosphodiesterase action

Sometimes hormones that are bound to

plasmalemma are taken into cell by endocytosis,

either for destruction or for further intracellular

action

mRNA produced by hormones that act

intracellularly is degraded



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Structure of the hypothalamus

The hypothalamus is the basal part of

the diencephalon below the thalamus Forms walls and lower part of the third

ventricle of the brain

It includes the optic chiasm, tuber

cinerum, infundibulum and mammillarybodies

The tuber cinerum

Part of the 3rd ventricle floor that extendsdownwards to the infundibulum

The lower part (median eminence) ishighly vascularised

The blood vessels drain into the pituitarystalk onward to the secondary plexus of

the anterior pituitary This vascular link with pituitary is called

the hypophysial portal system



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Hypothalamic nuclei Clusters of neurons that are symmetrically

located around 3rd ventricle Supraoptic and paraventricular nuclei cell

bodies whose axons extend into the medianeminence then the neurohypophysis

Supraopticoparaventriculohypophysial tract

Other groups include the ventromedial nuclei,arcuate nucleus, lateral tubal nuclei and thedorsomedial nuclei

Endocrine hypothalamus Neurosecretory neurons secrete

neurohormones (hypophysiotropic factors)

that regulate adenohypophyseal function These are elements of the parvocellular

neurosecretory system

The magnocellular system include thesupraoptic and paraventricular neurons whichsecrete oxytocin and vasopressin

Neurons of the parvocellular system convergetoward the pituitary stalk to form thetuberoinfundibular tract

They abut on the endothelium of the primarynexus of the portal system of the medianeminence link with adenohypophysis



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The medial basal hypothalamus contains the

hypohysiotropic area which extends from the

median eminence upwards and forwards through

the anterior hypothalamus to the suprachiasmatic

region

The endocrine hypothalamus linked to the CNS via

other neuronal elements

The information from CNS is delivered to

parvocellular neurosecretory system to the

pituitary portal system via the median eminence

link between CNS and the peripheral endocrine

system

The hypophysial portal system is the vascular link

between neurosecretory cells and the

adenohypophysis



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Hormones of the hypothalamus

The hypothalamus secretes hypophysiotropic

hormones these are stimulatory or inhibitoryfactors that control function of the pituitary

It also secretes neurosecretions oxytocin and

vasopressin (discussed under pituitary hormones)

Thyrotropin releasing hormone (TRH)

Stimulates release of thyroid stimulating hormone

from the pituitary

Composed of 3 AA residues pyroglutamic acid,

histidine and proline

The N-terminal amide is protected by cyclisation

while the carboxy terminal is modified by amidation

Synthesised in the medial part of the external layer

of the median eminence

Results from posttranslational cleavage of a larger

prohormone

The prohormone has several copies of the bioactivecompound which allows for amplification of

hormone production

Inactivated by a plasma petidase



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Somatostatin (somatotropin-releaseinhibiting hormone; SRIH)

Pituitary somatotropin release ispulsatile and is a result of interplaybetween two hormones of thehypothalamus a stimulatory factor

and an inhibitory factor SRIH or SRIF is a tetra-decapeptide (14

residues)

Released from secretory granules ofthe hypothalamus

Derived from a 28 residueprosomatostatin

Functions

Affects the brain and both the exocrine

and endocrine pancreas and the gut apartfrom inhibiting somatotropin release

Inhibition of somatotropin release isthrough direct action on somatotrophs



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Somatocrinin (Somatotropin release factor;SRF)

44 AA residues Shares sequence homologies to several gut

peptides of the secretin-glucagon family

The 1 to 29 peptide fragment has the samebioactivity as the entire compound

Gonadotropin releasing hormone (GnRH) A decapeptide with similar structure across

mammalian species

GnRH arises from and secretion is controlledby extrahypothalamic part of the brain

Its release is pulsatile

Constant administration leads todesensitisation of process responsible forgonadotropin release

The gonadotropins (LH & FSH) are synthesisedwithin the same gonadotroph afterstimulation by GnRH and modulation by

gonadal hormones The frequency of the GnRH stimulus

determines the proportions of LH and FSHwith a higher frequency promoting LHproduction while a lower frequency promotesFSH release




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Corticotropin-releasing hormone

Stimulates adrenocorticotropic hormone (ACTH orcorticotropin) release from the pituitary

Highly conserved 41 residue peptide

Prolactin release-inhibiting hormone (PIF)

Thought to be dopamine

There is also a prolactin-releasing factor that is

thought to be TRH

Melanocyte stimulating hormone release-

inhibiting factor

Thought to be dopamine

Release of hypophysiotropins usually follows a

circadian rhythm

The biological rhythm follows light cues with light

acting as a zeitgeber (time-giver)



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Feedback control of hypothalamus


Higher Brain Centres

Hypothalamus

Pituitary

Adrenal cortex Gonads

Ovary Testicles

Thyroid

ThyroxineTestosteroneOestradiolCortisol

Target tissues

Hypophysiotropic Hormones

ACTH FSH LH TSH

Long loopfeedback

Short-loop

feedback

Autoinhibition

(-)

(-)

(-)

(-)

(-)


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The pituitary gland

The pituitary is 0.5 to 1 g in weight

It is recessed within the stella turcica of

the sphenoid bone, beneath the

hypothalamus near the optic chiasm

Composed of tissues from 2 sources

Adenohypophysis (glandular or epithilial

hypophysis) is derived from an

invagination of the oral ectorderm of the

stomodeum (primitive mouth cavity)

called Rathkes pouch

Nuerohypophysis neural ectoderm of

the floor of the forebrain



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The pituitary gland

Adenohypophysis

Pars distalis

Pars tuberalis

Pars intermedia

Neurohypophysis

Pars nervosa

Infudibulum

Anterior lobe

Intermediate lobe

Posterior lobe

Neuro-intermediate lobe

Median eminence

Optic chiasm

Pars tuberalis

Pars distalisPars nervosa

Pars intermedia

Infundibular stem

PosteriorAnterior


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The pituitary gland

Size of each lobe depends on ecologicalniche the animal spp. occupies Animals that change colour rapidly have a

relatively large pars intermedia - MSHproduction

Pars nervosa small in aquatic animals butrelatively large in land animals vasopressin

production Hormonal output of the gland required for

successful adaptation to niche

Blood supply Superior and inferior hypophysial arteries

Anterior and posterior branches of thesuperior hypophysial artery penetratehypophysial stalk as well as hypothalamus

Pars distalis vascularised by hypophysial portalvessels that arise from capillary beds withinthe median eminence of the hypothalamusbrain pituitary axis

Pars nervosa receives blood supply from theinferior hypophysial artery

Adenohypophysial secretions released intoefferent portal veins to general circulation



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The pars nervosa contains neuronal axon endings

and pitiucytes

There are some non-granulated non-secretory cells

Cells of the pars distalis are classified based on

affinity to various dyes into basophils, acidophils

and chromophobes (See table below)

Cell Type Hormone Staining

characteristics

Corticotroph ACTH (Corticotropin) B

Thyrotroph TSH (Thyrotropin) B

Gonadotroph

FSH Gonadotroph FSH (Follitropin) B

LH Gonadotroph LH (Lutropin) B

Lactotroph

(mammotroph)

PRL (Prolactin) A

Somatotroph STH (Somatotropin) A


The pituitary gland


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Hormones of the pituitary

The pituitary secretes 7 peptidehormones (FSH, LH, STH, TSH, ACTH, PRL

& melanocyte stimulating hormone) and2 neurohypophysial peptide hormones(vasopressin and oxytocin) The later two are secreted by neurons of

the neurohypophysis whose cell bodiesoriginate in the hypothalamus

The hormones can be classified into 4groups based on structural similarityand evolutionary origin Somatotropin & prolactin

Bear sequence similarity and are related toplacental lactogen (somatomammotropin)

Thyrotropin, follitropin & lutropin Glycoproteins that are also related to

chorionic gonadotropin (of placental origin)

Melanotropin & corticotropin

Sequence similarity and overlapping action Oxytocin & vasopressin

Nuerohypophysial hormones that arestructurally related to each other



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Somatotropin Prolactin

Somatotropin (STH)

Accounts for 4-10 % of weight ofanterior pituitary

Circulates in plasma complexed to oneor more binding proteins

Basal level in blood 1-5 ng ml-1

Spontaneous episodes of STH releaseoccurs during 24 hr period

Controlled by somatocrinin &

somatostatin Polypeptide synthesised by acidophilic

somatotrophs of the pars distalis

Synthesised as a prohormone that iscleaved to yield a 191 AA protein with

two internalS-S- bridges

Shares 161 AA homology withplacental lactogen



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Somatotropin

Role

Protein anabolic hormone

Enhances AA incorporation into

protein

Increases extracellular collagen

deposition

Affects ion balance

Major effects mediated indirectly

through IGFs released from the liver

Major hormone that controls growth

Deficiency leads to dwarfism

(hypopituitary or Larons dwarfism)

while over production leads to

gigantism



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Prolactin (PRL) Hormone of maternity responsible for

mammary growth, development andlactogenesis

Works in concert with other hormones such asoestrogens, insulin, glucocorticoids,progesterone and somatotropin

During pregnancy and early lactation PRL

producing cells constitute 50 % ofacidophilesin anterior pituitary

Production controlled by oestrogens thatcontrol PRL gene expression and increasenumber of secreting cells

There is an increase in PRL secretion at

puberty, progressive increase during pregnancyand a peak at term

Luteotropic in some species in that itstimulates progesterone synthesis andsecretion

Controls production of crop sac milk in pigeonsand doves, may also control testicular function

Secretion episodic with nighttime surge, halflife 15 20 minutes

Release also associated with nursing

Controlled by PRL release inhibiting factor



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Glycoprotein hormones

3 glycoprotein hormones from the anteriorpituitary Thyrotropin (Thyroid stimulating hormone

TSH)

Follicle stimulating hormone &

Luteinising hormone

Contain several covalently linkedcarbohydrate moieties at one or morepositions within their structure

Composed of two chains & subunitsthat are independently synthesised

The -subunits are the same for all three

hormones within a species They are composed of 92 residues in humans

(96 in other spp)

They may have similar AA residues but the N-linked oligasaccharide may be different

There 71 AA residues that are conservedacross spp.

10 of the half-cystine residues are also highlyconserved with 5 disulphide bridges which areidentical across spp.



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The -subunits are related but differ moresubstantially in AA sequences 110-111 residues in LH

112-118 residues in TSH

117-121 residues in LH/FSH

145 residues in chorionic gonadotropin

12 cysteine residues at highly conservedpositions (6 disulphide bridges similartertiary structure)

Intersubunit contact similar acrosshormones but subunit to tissue contactdifferent hormone specificity (-subunit)

Glycosylation of units is a posttranslationalevent Sugars include D-mannose, D-galactose, L-

fucose, N-acetylneuraminic acid, D-glucosamine, N-acetylated-D-galactoseamine

The -subunit contains 2 oligosaccharide units

that are N-linked to asparagine residues May also contain O-sulphated hexosamine

attached serine

Carbohydrate moieties important for receptorsignal transduction



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Thyrotropin (thyroid stimulating

hormone TSH) Stimulates production of thyroxine

(T4) and triiodothyronine (T3)

Synthesised by thyrotrophs of the parsdistalis

Controlled through negative feedbackby T3 & T4

Also plays role in metamorphosis(amphibians) & thermogenesis(mammals)

Lutropin (Luteinising hormoneLH) Stimulates formation of corpora lutea

& ovulation in the female

Works in concert with FSH to stimulate

interstitial cells of the Leydig testes &stimulates development of 2characteristics



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Follitropin (Follicle stimulating

hormone FSH) Increases follicular growth and

spermatogenesis

Stimulates the early stages of

ovarian follicular growth and earlystages of spermatid maturation

In males

Increases LH receptor population

Acts in concert with LH to stimulatespermatogenesis

Stimulates synthesis of sertoli cellandrogen-binding protein

In females

Interacts with granulosa cells ofdeveloping follicle in cAMP mediatedmanner



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Proopiomelanocortin corticotropin

& melanocortin

Share structural similarity Corticotropin (Adrenal cortical-

stimulating hormone- ACTH or

adrenocorticotropin) is synthesised

corticotrophs of the pars distalis Melanocortin (Melanocyte stimulating

hormone MSH) is synthesised by

melanotrophs of the pars intermedia

They are both derived fromproopiomelanocortin with enzymes in

the pars distalis cleaving the ACTH

sequence while those in the pars

intermedia cleave the MSH sequence

They cross stimulate (weakly though)

each others target cells



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Corticotropin 39 AA residues

Secreted by basophils/chromophobes of parsdistalis

Stimulates steroidogenic tissues of theadrenal cortex

Major structural differences in ACTH acrossspecies are usually found in residues 24 to 33with some species only differing the residues31 & 33

Stimulates cortisol and corticosterone whichare involved in carbohydrate metabolism

Melanocortin 13 AA residues

Secreted by cells in the pars intermedia

SharesMet-Glu-His-Phe-Arg-Trp-Gly-sequence with ACTH

Responsible for coloration in most vetebrates Pars intermedia absent in humans but present

in animals that need to change color


Proopiomelanocortin corticotropin

& melanocortin


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Neurohypophysial hormones

2 nonapeptides oxytocin and vasopressin which

are separately synthesised in neurohypophysialneurons whose cell bodies are located in pairedparaventricular (oxytocin) or supraoptic (presso-)nuclei of the hypothalamus

Part of group of 12 related peptides found in theanimal kingdom

4 related to vasopressin 8 related to oxytocin

Differ on position 3, 4 & 8 which affects activityand affinity

Derived from the prohormones preoxyphysin andprepressophysin

Vesicles containing hormones travel byaxoplasmic flow to axon terminal in the parsnervosa

Hormones linked to other proteins Oxyphysin for oxytocin

Pressophysin for vasopressin Hormone transport

Consist of nine AA residues folded into a ringthrough a disulphide bridge linking position 1 and6 leaving a tripeptide side chain



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Oxytocin Arginine vasopressin

Tyr

Ile

Glu

Agn

Cys

Pro

Glycinamide

Leu

Cys 1

3

5

2

4

7

6

9

8

Phe

Arg (Lys in pigs)


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Oxytocin Plays transitory role

Milk release (letdown)

Uterine contraction

Vascular smooth muscle action

vasodilation and vasoconstriction Maternal behaviour

Mating behaviour

Feeding behaviour

Vaospressin Osmoregulation

Blood volume pressure regulation

Promotes movement of water and Na+ions across membranes of the distal

tubule Contraction and relaxation of some

smooth muscles


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Calcium homeostasis

Ca2+ is a very important mineral Blood clotting

In concert with Na+ and K+ in creatingtransmembrane potential

Signal transduction

Stimulus secretion/ stimulus responsecoupling

3 hormones Parathyroid hormone (parathormone)

Calcitonin

1.25-dihydroxyvitamin D3

Parathormone (PTH) Synthesised as preproPTH (115 AA) which

is cleaved to proPTH (90 AA) and then toPTH (84 AA) in parathyroid gland

Deletion of the 2 AA at the N-terminusleads to loss of functionality

2 mechanisms of action One leads to cAMP formation

The other leads to IP3/DG formation

Two separate G proteins involved

Action mediated by Vit D3



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Calcium homeostasis

PTH Secreted through vesicular exocytosis

Controlled by circulating levels of Ca2+

Major roles Bone mineral metabolism

Renal reabsorption of Ca2+

Renal excretion of PO43-

Intestinal absorption of Ca2+

Control of Vitamin D3 synthesis

Calcitonin 32 AA withS S bridge between AA1

and 7

Prolinamide carboxyterminal group Controlled by circulating levels of Ca2+

The c-terminal prolinamide, thedisulphide bridge and the entire 32 AArequired for action

Calctonin receptor can bind to different Gproteins depending on cell cycle leadingto different responses in different tissues

Calcitonin receptor and PTH receptorrelated and unique



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Ca2+ Homeostasis

Calcitonin

Secreted by parafollicular cells of thethyroid gland

Major roles are Bone mineral metabolism

Control of satiety

Vitamin D3 regulation Vitamin D3

Synthesised in the skin in the presence ofsunlight through a photo-isomerisationstep followed by thermal-isomerisation

Major roles Intestine Ca2+ absorption and translocation

of PO43-

Bone mineralisation

Kidney tubular reabsorption of Ca2+

Pregnancy

Controlled by blood PO43- levels thatreduce activity of 1--hydroxylase whileCa2+ increases it



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Ca2+ Homeostasis

Vit D3 Interacts with target tissue nuclear

receptors to activate transcriptionaland translational events

Lag time of 2 hours to showeffects

Proteins induced include Ca2+

binding protein

Ca2+

channels activated in a non-genomic manner

Receptor family features

Ligand-binding domain at c-terminus

DNA-binding domain the middle Variable n-terminus that helps select

between potentially responsive genes



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Vitamin D synthesis


Sunlight

Skin surface

Epidermis

Dermis

7-dehydrocholesterol (from liver)

Previtamin D3

Cholecalciferol

(Vitamin D3)

Luminsterol3Tachysterol

Thermal isomerisation

Photoisomerisation

Binding proteinsBinding protein-

cholecalciferol

Systemic circulation


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The endocrine pancreas

Composed of islets of tissue dispersedamong the much larger exocrine

pancreas

Islets of Langerhans (described 1869)

Constitute 1 2 % of pancreatic mass Four key cell types

cells (glucagon); cells (insulin); D cells

(somatostatin) & F cells (pancreatic

polypeptide)

All involved in glucose homeostasis (&

a lot of other things)

Glucose homeostasis involves a push

pull system that controls glucose flux

in an out of extracellular space



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Insulin

Dominant metabolic regulator

Deficiency leads to runaway glucoseproduction, lipolysis, ketogenesis,proteolysis !

Excess leads to hypoglycemia, brain

failure ! Polypeptide with two chains; A (21 AA

with 6 to 11 intrachain disulphidebridge) & B(30 AA). The two are linkedthrough 2 interchain bridges

Interspecies differences at A (8, 9 & 10)and B (30)

Differences do not reduce potency butmay antigenic in some individuals

Derived from proinsulin where the twochains are linked through connectingpeptide



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Insulin

Proinsulin derived from a precursor

The c-terminus and connecting

peptide of these precursors highly

variable linked to evolution of

insulin like growth factors Complexed with Zn in islet cells

Degraded in liver and kidney with a

half-life of 5 minutes

Hepatic glutathione insulindehydrogenase disrupts hormone into

separate chains that are then degraded

independently



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Insulin

Physiological role The only hormone that lowers blood

glucose levels

Promptly released from islets inresponse to elevated glucose levels

Interacts with several tissue typeshepatic, muscle, adipose (why?)

Enhances uptake of glucose by cells

Activates glycogen synthetase lead toglycogen synthesis in the liver

In adipose tissue glucose uptake leadsto increased catabolism of sugar toglycerol

Stimulates active transport of glucose& AA in muscle cells

Protein synthesis enhanced Plays role in K+ homeostasis through

increased uptake



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Insulin

Mechanism of action Insulin receptor

2 subunits & 2 subunits held

together by inter and intrachain

disulphide bridges

All units glycosylated

has the insulin binding domain

(outside) while the is

transmembrane with the c-terminus

having a tyrosine kinase domain

Insulin binding activates

autophosphorylation of subunit to

produce an active tyrosine kinase

Complex is deactivated byinternalisation of ligand bound

receptor receptor recycled



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Insulin


TP

TYR- PROTEIN

P

P

ADP

P-TYR-PROTEIN

Insulin

action


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Insulin

Second messengers

Intrinsic tyrosine kinase activity

May be via Ca2+

Other second messengers

suspected including inositol glycansand diacylglycerol

Glycogen formation controlled by

glycogen synthetase

Dephosphorylated active

Glycogenolysis hepatic

phosphorylase

Phosphorylated active

Insulin may act by maintaining

dephosphorylated state of both

enzymes Why?



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Glucagon

Single chain polypeptide (29 AA

residues)

Similar to secretin, gastric inhibitory

peptide and vasoactive intestinal

peptide Derived from large preprecursor that

undergoes several posttranslational

modification

Similar among mammals, in birdsresidue 28 (asparagine) is replaced

with serine while in ducks an

additional residue is also substituted

(serine with threonine at position 16)



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Other pancreatic hormones

Somatostatin Control of glucagon and insulin release

mediated by electrical potential andother peptides including somatostatin

Local paracrine role given juxtapositionof D cells to and cells

Derived from a prohormone

Also controls GIT function andmovement of nutrients from the gut

Pancreatic polypeptide

36 AA, variable sequence across spp Functions not clearly elucidated

Lowers liver glycogen and stimulateslipolysis

Produced from F cells and participatein reciprocal control of secretions ofendocrine pancreas



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Hormones of the GIT

Many hormones of the GIT fall under

families of related hormones that shareoverlapping structure and function

Primarily concerned with digestion andmovement of food products in the GIT

Synthesised from a system of clear(enterochromaffin, argyrophil, orargentaffin) cells

These are the dispersed endocrinesystem since cells are scattered fromstomach to colon

Together with pancreatic secretionscalled gastroenteropancreatic hormones

Why dispersed?

Hormone release regulated by integratedsampling of contents

One surface of enterochromaffin like cellis in contact with luminal contents



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Hormones of the GIT

Families

Gastrin gastrins (!), cholecystokinins(CCK)

Secretin secretin, glucagon,vasoactive intestinal peptide (VIP),gastric inhibitory peptide (GIP)

Others motilin, somatostatin,substance P, neurotensin etc

Gastrin The five c-terminal amino acids of

gastrin & CCK are the same andconstitute the biologically activefragment

The terminus is amidated

Overlapping action of hormones

Minimum active fragment is the last 4AA

Amino terminus influences potencyand specificity



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Hormones of the GIT

Gastrin

Four molecular forms

Preprogastrin which is not found in

circulation

Big gastrin (gastrin-34, orprograstrin); Little gastrin (gastrin-

17, physiologically active); Mini-

gastrin (gastrin-14, may be

degradation product) Secretin

Secretin (27 AA) is similar to

glucagon (29 AA) in 14 positions

Similar to VIP and GIP



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Hormones of the GIT

Physiological roles

Stimulate secretion of enzymes

necessary for digestion

Regulates acid or base secretion for

pH regulation

Regulates peristaltic movement of

digesta gut motility

Stimulate release of hormones from

the pancreas Satiety signals to the CNS affects

feeding behaviour)

Released in response to specific

chemical stimuli

H+ ions, certain AA, FFAs and sugars



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Hormones of the GIT

Gastrin

Released from antral mucosa of thestomach and also from the duodenalmucosa

Primary stimulus from secretion is food

Peptide fragments, AAs, FFAs

Somatostatin and VIP producing cells locatedin close proximity paracrine control

Stimulates HCl and pepsinogen secretion,lower oesophageal sphincter pressure,relaxation of pyloric sphincter, pancreatic

enzyme secretion etc

Secretin

Released in response to acid in the upperduodenum

Stimulates bicarbonate (HCO3-

) releasefrom pancreas

Potentiates CCK in stimulating pancreaticenzyme secretion



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Hormones of the GIT

CCK

Causes contraction and emptying of the gallbladder in response to presence of food (esplipids) in duodenum

Release of pancreatic enzymes

33 AA but can exist in other forms

7th carboxyterminus AA is sulfated

Inhibition of gastric emptying Potentiation of secretin induced bicarbonate

secretion

GIP 43 AA

Inhibits gastric acid secretion and is insulinotropic

Activates lipoprotein lipase (adipose tissues),inhibits glucagon induced lipolysis and potentiatesinsulin-induced incorporation of FFA to TAGs

VIP Entire 28 AA required for action

Well conserved in animals

Mediates the descending relaxation component ofperistalsis

Relaxes a variety of smooth muscles

Vasodilatory and hypotensive

Also has neurocrine action



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Thyroid hormones

Functional components of the thyroid gland arethe individual thyroid follicles cuboidal epithelium arranged as a single layer

surrounding a lumen that contains colloid material

Clear cells found in thyroid are a source ofcalcitonin

Follicular cells synthesise a protein calledthyroglobulin Released into colloid space through vesicular

exocytosis

Thyroglobulin is a substrate for tyrosine iodination

Endocrine stimuli lead to follicular cells engulfing

colloid material phagocytosis The colloid in endocytotic vesicles degraded to

yield thyroid hormones that enter extracellularspace

Release also controlled by sympathetic neurons allow for rapid short-term alteration in rate of

hormone secretion

Thyroid hormones are covalently complexed toiodide

Iodine not readily available in terrestrialenvironments so cellular mechanisms haveevolved for uptake of iodine


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Thyroid hormones

Cells able to trap iodide and transport it againstan electrical gradient

A Na+ - I- cotransport is inserted into thebasolateral membrane of the thyrocyte - 2 activetransport system (for more on this visithttp://edrv.endojournals.org/cgi/content/full/24/

1/48) activity dependent on the Na+ gradient created by

the Na+/K+ - ATPase

aka sodium-iodide symporter or solute carrier family 5

member 5 (a member of the sodium/solute symporterfamily)

2 Na+ ions for every I-

The iodide is converted to an oxidised species bya peroxidase species incorporated into tyrosyl groups of

thyroglobulin to produce monoiodotyrosyls anddiiodotyrosyls

the iodinated tyrosyls undergo oxidative couplingto produce T4 and a smaller amount of T3 in colloidspace
http://edrv.endojournals.org/cgi/content/full/24/1/48http://edrv.endojournals.org/cgi/content/full/24/1/48http://edrv.endojournals.org/cgi/content/full/24/1/48http://edrv.endojournals.org/cgi/content/full/24/1/48http://edrv.endojournals.org/cgi/content/full/24/1/48


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Thyroid hormones

The thyroglobulin gets engulfed & digestedto yield free T4 and T3 which diffusethrough basolateral membranes

Unused iodinated tyrosyls are deiodinated& recycled within the cell

Secretion regulated through action orthyrotropin (TSH) &TRH

T4 is the dominant form which seems toserve some function in somedevelopmental stages & feedback control

on the hypothalamus T3 seems to be the more biologically active

The hormones are water-insoluble & aretransported attached to specific bindingproteins in plasma & cytosol nuclearreceptors

In plasma thyroxin binding prealbumin& thyroxin binding globulin TBPA a homotetramer with 2 T4 binding

sites


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Thyroid hormones

Blood vesselIodine

NIS

I-TG synthesis

TGI

Follicular lumen(colloid space)

Oxidative coupling

DIT

DIT DITMIT

T4 T3

T4, T3

Endocytosis

Colloid droplet

2 lysosome

LysosomeT4, T3

Iodotyrosines

Deiodinase

Recycle

GlucoseTSH

Pentose cycle

ATPcAMP

Peroxide generatingsystem

Peroxidase


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Thyroid horomonesPhysiological

roles

Thyroid hormones influence manybodily functions direct & permissive actions

exert effects in almost all body tissuesthroughout the life of an individual

Growth and development secretion of somatotropin reduced in the

absence of thyroid hormones

Required for both production andsystemic effects of somatotropin

stimulate differentiation through actionon hyalorunidase acticity

play major role in mammary gland growth

and development together with prolactin required for normal growth of the brain

stimulates nerve growth factorbiosynthesis


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Thyroid hormones

Thermogenesis stimulate mitochondrial oxygen consumption &

ATP production

20 40 % of this consumed through Na+ activetransport & heat generation homoetherms

T3 induced increase in Na+/K+ ATPase due to

increase in enzyme sites enzyme controlled at transcriptional, translational

and posttranslational levels

Diet and TH function diet induced thermogenesis result from higher T3

circulation

fasting leads to reduced hepatic T3 receptors response variable

possibly couples feed restriction with reduction infrequency and severity of age-related illnesses

Permissive actions required for action of other hormones

exert action at genome level inducing synthesis ofvarious proteins which are substrates in the actionof other hormones

synergy with glucocorticoids in enhancingsynthesis of STH

Enhance STH function in the brain


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Summary

List if thyroid hormone functions Feedback inhibition of pituitary TSH secretion

Permissive action to other hormones lipolytic response of adipose tissue to other

hormones

required for STH & prolactin function & synthesis

Increase activity of sympathoadrenal system

Regulate basal metabolic rate increase mitochondrial oxidative

phosphorylation

Required for hepatic conversion of carotenes

to Vitamin A Bone & nervous system growth and

maturation

Increase intestinal glucose uptake

Increase red blood cell Ca2+ ATPase activity

Induce enzyme synthesis Induce synthesis of proteins other than

enzymes


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Thyroid hormones mechanism of

action

Analogous to action of steroid

hormones

Thyroid receptors are intranuclearproteins (ligand-activated transcription

factors) with domains for binding T3,

DNA & forming homo- or

heterodimers with other proteins Two receptor types1, 1 & 2 with

2 inhibiting the transcriptional effects

of the other three

Also act on a number of cellularreceptor sites including plasmalemma,

mitochondria etc


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Hormones of the adrenal glands

Epinephrine & norepinephrine are

hormones of the chromaffin tissue of theadrenal glands & sympathetic neurons,respectively

similar in structure and biological actionreferred to as the sympathoadrenal system

both sympathetic neurons and chromaffintissue are structural and functionalcomponents of the autonomic nervoussystem (ANS)

the parasympathetic system is concerned

with the vegetative or resting states of thebody GIT motility, digestion, storage of nutrients etc

the sympathetic system is concerned withmore active states of the body includingmanaging stress Flight or fight

enhance blood flow to brain and muscle,shunting blood away from skin, digestive tract,kidney

increased force and rate of heartbeat


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Adrenal chromaffin tissue

Adrenal gland composed of tissuesfrom two distinct embryonic cellulartypes chromaffin tissues (catecholamine

synthesis) derived from neural crest

steroidogenic tissue derived frommesoderm

in mammals chromaffin form themedulla surrounded by thesteroidogenic cortex

Within chromaffin tissue there are twocellular types adrenaline (A) and noradrenaline (N)

storing cells

Contain granules composed of

catecholamines, adenine nucleotides(mainly ATP), proteins and lipids

The A cells contain more glycoproteins

Ratio of cells differs with species


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Synthesis, chemistry & storage

Phenylalanine

Tyrosine

Dihydroxyphenylalanine (DOPA)

Dopamine

Norepinephrine(primary amine)

Epinephrine

(N-methylated secondary amine)

Phenylalanine hydroxylase

Tyrosine hydroxylase (rate limiting step)

L-aromatic amino acid decarboxylase

Dopamine -hydroxylase (DBH)

Phenylethanolamine N-methyltransferase

(PNMT)


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Synthesis, storage, chemistry

Synthesis Pathways seem to be identical in all tissues that

express them

Number of steps depend on terminal product tobe secreted

In species where chromaffin tissues are separated

from steroidogenic tissue the main product is NEbut in mammals the main product is E

Storage catecholamines stored within granules wherein

they are complexed with ATP, a specific proteincalled chromagranin and DBH (enzyme)

Storage vesicles released through Ca

2+

-dependentstimulus-secretion coupling with all contents ofvesicles released through vesicular exocytosis

Metabolism two enzymes catecholamine-o-

methyltransferase (COMT) & monoamine oxidase(MAO) allow for rapid removal of catecholamines

from circulation and synaptic cleft lead to production of normetanephrine sulfate or

glucuronide & metanephrine sulfate ofglucuronide


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Mechanism of action

Receptors

two types in sympathoadrenalsystem adrenergic & choligernic

Adrenergic recptors two types that differ in response to

different sympathetic amines & adrenoceptors

AR has the following potency

ranking Epinephrine >norepinephrine > isoproterenol (ISO)

responsible for smooth musclecontraction

AR ISO > E > NE

smooth muscle relaxation

Lead to up to 9 different subfamilieslocated in different tissues


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Adrenoceptor signal transduction

AdenylateCyclase

Phospholipase C

Phosphoinositides

1221

IP3 & DG

Cellular response

ATP cAMP

(-)(+) (+)


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Lipolytic action

Adenylate

Cyclase

ATP cAMP

Inactive hormonesensitive lipase

Active hormonesensitive lipase

TAGsFFAs &

Glycerol

Epinephrine

receptor

ACTH

receptor

Blood

Adipocyte

membrane


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Functions

Function modulated by gonadal steroids,adrenal steroids and thyroid hormones

Maintain constancy of internalenvironment

Activated in anticipation of events that

might adversely affect the individual Response to stress

Role in intermediary metabolism Carbohydrate metabolism

E stimulates hepatic glycogenolysis, muscle lactic

acid production, hepatic gluconeogeneis, inhibitsinsulin secretion while increasing glucagonsecretion, stimulate numerous processes thatelevate blood glucose levels

Fat metabolism stimulate lipolysis

FFAs used as energy source (glucose sparingaction) & as a source of glucose

Protein metabolism reduced proteolysis


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Functions

Thermogenesis both shivering and non-shivering

(chemical) thermogenesis

Cardiovascular system increase force and rate of heartbeat

Blood shunted from skin, kidney, mucosa,connective tissue to areas of higherdemand

spleen capsule contracted to increaseerythrocytes in circulation higheroxygen uptake

Reduced clotting time

Respiratory system

Increased respiratory volume throughrelaxation of bronchial muscles

Stress response


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Adrenal steroid hormones

synthesis & chemistry

Cholesterol (27 C) is the precursor of allsteroid hormones

A 6 C fragment is cleaved from the side

chain in mitochondria to produce a 21 Csubstance (pregnenolone) which is movedto endoplasmic reticulum

Key enzymes - desmolase system(cytochrome P450scc)

Several key intermediates lead to formationof steroid hormones

3 groups Glucocorticoids e.g. cortisol

Mineralocorticoids e.g. aldosterone

Androgens

Presence of a double bond betweenposition 4 & 5 & presence of a keto groupat 3 of A ring essential for biological activityof adrenal steroids


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Synthesis
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Adrenal steroids

Control of synthesis adrenal glucocorticoids controlled by

andrenocorticotropin (ACTH), aldosterone

controlled by the renin-angiotensinsystem

Physiological roles Glucocorticoids

Intermediary metabolism Carbohydrate, lipid and protein metabolism

increase synthesis of enzymes involved ingluconeogenesis

anabolic to the liver, catabolic to skeletal muscle& adipocytes

excessive production antagonistic to insulin

permissive action required for function of sympathoadrenal system

necessary for catecholamin synthesis anddecrease their degradation

Permit lipolytic activity of catecholamines

Permissive action also helps maintain bodytemperature


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Adrenal steroids

Glucocorticoids

Reproduction

involved in process of parturition

required for lactogenesis in some species

Nervous system

normal development of CNS in the foetus

structural integrity of the adult brain

Anti-inflammatory and

immunosuppressive inhibit inflammatory & allergic reactions

in doses higher than physiological

Negatively affects immunity

The general adaptation syndrome

modulates response to stress

Ranking & population control in

gregarious species


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Adrenal steroids

Aldosterone

Regulates Na+ homeostasis and indirectly

volume homeostasis

essential for life (cf parathormone)

Na+/K+ homeostasis


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The gonadal steroids - synthesis


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Gonadal steroids - Functions

In adult males production of gonadal

steroids is generally uniform while it is

cyclic in females Organisational roles

testosterone responsible for organisation

of internal & external genitalia &

differentiation of the brain into the male

type

Activational roles

associated with acute release of pituitary

gonadotropins & sexual behaviours

associated with reproductive processes

Reversible, repeatable and not associated

with any particular phase of development


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Gonadal steroids

Activational roles

Control of gonadotropin secretion

via receptors in the preoptic area infemales

constant in males leading to constant

GnRH production

aggressive behaviour (androgens),mood & the menstrual cycle,

gender identification, puberty etc


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Gonadal steroids (Androgens)

Primary locus of action Physiological response

Prepubertal

Accessory glands Wolffian duct differentiation & growth

External genitalia Growth & differentiation (scrotum &

penis)

Pubertal

Skeletal muscle Masculine body growth & physique

(Na+, K+ & H2O retention)

Bone Epiphyseal closure (Ca2+, SO4-2, PO4-3

retention)

Vocal cords Voice change

Skin Hair growth (in some areas) & loss

(forehead), sebaceous gland growth

Testis Sertoli cell maturation & androgen

binding protein synthesis,

spermatogenesis

External genitalia Penile and scrotal growthAccessory glands Growth & maturation of accessory

glands

Central nervous system Libido increased

Hypothalamo-pituitary

axis

Inhibition of LH secretion


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Gonadal steroids ovarian steroids

Primary site of action Physiological action

Oestradiol

CNS Maintains libido & sexual

behaviour

Pituitary Feedback effects on gonadotropin

secretion, increase pituitary TRH &GnRH recptor number, increases

oxytocin production

Ovary Required for ovum maturation

Vagina Causes proliferation &

cornification of the mucosa

Oviducts Growth & maturation in prep forgamete transport

Uterus

Cervix Increases mucus secretion

Endometrium Increases blood flow,

prostaglandin biosynthesis,

oxytocin receptors at term,

decidualisation response

Myometrium Synthesis of contractile smooth

muscle proteins, increase

sensitivity to oxytocin

Mammary glands Fat accretion, ductule & stromal

growth & development


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Ovarian steroids

Primary site of action Physiological action

Oestradiol

Skin Induces sebaceous gland secretion,

stimulates axillary and pubic hair growth

General body effects Causes H2O and Na+ retention, weight gain

& female type fat distribution, maintains

bone mineral deposition

Liver Causes hepatic angiotensinogen & thyroid-

binding globulin production

Blood Decreases blood cholesterol production

Progesterone

CNS Increases sexual receptivity, sometimes

inhibits gonadotropin release

Oviducts Causes growth and development for gametetransport

Uterus

Endometrium Stimulates growth & devt in prep for

pregnancy, decreases oestrogen receptor

number

Cervix Increases mucus consistency

Myometrium Anti-oestrogen effects, maintenance of

pregnancy

Vagina Inhibits oestrogen-induced vaginal

cornification

Mammary glands Inhibits prepartum lactogenesis

General body effects Rise in basal metabolic rate (thermogenesis)


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Hormones of the pineal gland

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AS211 Endocrinology Lecture Notes1

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