Chapter 11

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Chapter 11

Endocrine Glands -Secretion & Action of

Hormones

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Chapter 11 Outline

Overview Chemical Classification of Hormones Hormonal Actions & Interactions Mechanisms of Hormone Action Pituitary Gland Adrenal Gland Thyroid Gland Islets of Langerhans Miscellaneous Glands & Hormone Autocrine & Paracrine Regulation

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Overview

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Endocrine Glands

Are ductless & secrete hormones into bloodstream

Hormones go to target cells that contain receptor proteins for it

Neurohormones are secreted into blood by specialized neurons

Hormones affect metabolism of targets

Fig 11.1

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Chemical Classification of Hormones

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Chemical Classification of Hormones

Amine hormones are derived from tyrosine or tryptophan Include NE, Epi, thyroxine, melatonin

Polypeptide/protein hormones are chains of amino acids Include ADH, GH, insulin, oxytocin, glucagon, ACTH,

PTH Glycoproteins include LH, FSH, TSH Steroids are lipids derived from cholesterol

Include testosterone, estrogen, progesterone & cortisol

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Fig 11.2

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Chemical Classification of Hormones continued

Steroid & thyroid hormones are lipids Can diffuse into target cells

The 2 major thyroid hormones are shown in Fig 11.3

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Prohormones & Prehormones

Prohormones are precursors of hormonesE.g. proinsulin

Prehormones are precursors of prohormonesE.g. preproinsulin

Some hormones are inactive until activated by target cellsE.g. thyroxine (T4) is inactive until converted

to T3 in target cells

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Hormonal Actions & Interactions

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Common Aspects of Neural & Endocrine Regulation

Both NS & endocrine system use chemicals to communicate

Difference between NTs & hormones is transport in blood & more diversity of effects in hormone targets

Some chemicals are used as hormones & NTs Targets for both NTs & hormones must have

specific receptor proteins Must be way to rapidly inactivate both

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A tissue usually responds to # of hormones 2 hormones are synergistic if work together to

produce an effectProduce a larger effect together than

individual effects added together A hormone has permissive effect if it enhances

responsiveness of a target organ to 2nd hormone

If action of 1 hormone inhibits effect of another, it is antagonistic

Hormone Interactions

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Hormone Levels & Tissue Responses

Half-life is time required for blood level to be reduced by halfRanges from mins to hrs for most (days for

thyroid hormones) Normal tissue responses are produced only

when hormones are in physiological range High (pharmacological) doses can cause # of

side effectsProbably by binding to receptors of other

hormones

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Priming effect (upregulation) occurs when a hormone induces more of its own receptors in target cells Results in greater response in target cell

Desensitization (downregulation) occurs after long exposure to high levels of polypeptide hormone Subsequent exposure to this hormone produces

a lesser response Due to decrease in # of receptors on targets Most peptide hormones have pulsatile secretion

which prevents downregulation

Hormone Levels & Tissue Responses continued

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Mechanisms of Hormone Action

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Mechanisms of Hormone Action

Target cell receptors show specificity, high affinity, & low capacity for a hormone

Lipid hormones have receptors in target's cytoplasm &/or nucleus because can diffuse thru plasma membrane

Receptors for water-solubles are on surface of target cell

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Hormones That Bind to Nuclear Receptor Proteins

Lipid hormones travel in blood attached to carrier proteins They dissociate

from carriers to pass thru plasma membrane of target Receptors are

called nuclear hormone receptors

Fig 11.4

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Nuclear Hormone Receptors

Serve as transcription factors when bound to hormone ligands Activate transcription

Constitute a "superfamily" composed of steroid family & thyroid hormone family (which includes vitamin D & retinoic acid)

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Nuclear Hormone Receptors

Have ligand (hormone)-binding & DNA-binding domains Binds hormone & translocates to nucleus Binds to hormone-response element (HRE) on DNA

located adjacent to target gene

Fig 11.5

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Mechanisms of Steroid Hormones

HRE consists of 2 half-sites

2 ligand-bound receptors have to bind to each HRE (dimerization) This stimulates

transcription of target gene

Fig 11.5

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Mechanism of Thyroid Hormone Action

Thyroid secretes 90% T4 (thyroxine) & 10% T3

99.96% of T4 in blood is bound to carrier protein (thyroid binding globulin - TBG)

Only free can enter cells, so bound is reservoir

T4 converted to T3 inside cellT3 binds to receptor protein located in

nucleus

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Mechanism of Thyroid Hormone Actioncontinued

T3 & receptor bind to 1 half-site

Other half-site binds retinoic acid Two partners form

heterodimer that activates HRE Stimulates

transcription of target gene

Fig 11.7

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Hormones That Use 2nd Messengers

Water soluble hormones use cell surface receptors because cannot pass through plasma membrane Actions are mediated by 2nd messengers Hormone is extracellular signal; 2nd

messenger carries signal from receptor to inside of cell

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Mediates effects of many polypeptide & glycoprotein hormones

Hormone binds to receptor causing dissociation of a G-protein subunit

Adenylate Cyclase-cAMP

Fig 11.8

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G-protein subunit binds to & activates adenylate cyclase Which converts ATP into cAMP

cAMP attaches to inhibitory subunit of protein kinase

Adenylate Cyclase-cAMP continued

Fig 11.8

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Inhibitory subunit dissociates, activating protein kinase Which phosphorylates enzymes that produce

hormone’s effects cAMP inactivated by phosphodiesterase

Adenylate Cyclase-cAMP continued

Fig 11.8

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Serves as 2nd messenger system for some hormones Hormone binds to surface receptor, activates G-protein,

which activates phospholipase C

Phospholipase-C-Ca2+

Fig 11.9

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Phospholipase C splits a membrane phospholipid into 2nd messengers IP3 & DAG IP3 diffuses through cytoplasm to ER

Causing Ca2+ channels to open

Phospholipase-C-Ca2+

Fig 11.9

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Phospholipase-C-Ca2+ continued

Ca2+ diffuses into cytoplasm & binds to & activates calmodulin

Ca2+-Calmodulin activates protein kinases which phosphorylate enzymes that produce hormone's effects

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Epi Can Act Via Two 2nd Messengers

Fig 11.10

11-31

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Tyrosine Kinase 2nd Messenger System

Is used by insulin & many growth factors to cause cellular effects

Surface receptor is tyrosine kinase Consists of 2 units

that form active dimer when insulin binds

Fig 11.1111-32

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Tyrosine Kinase 2nd Messenger System

Activated tyrosine kinase phosphorylates signaling molecules that induce hormone/growth factor effects

Fig 11.1111-33

Pituitary Gland

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Pituitary Gland

Pituitary gland is located beneath hypothalamus at base of forebrain

Fig 8.16

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Pituitary Gland continued

Is structurally & functionally divided into anterior & posterior lobes

Hangs below hypothalamus by infundibulum

Anterior produces own hormones Controlled by

hypothalamus Posterior stores &

releases hormones made in hypothalamus Fig 11.12

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Anterior Pituitary

Secretes 6 trophic hormones that maintain size of targets High blood levels

cause target to hypertrophy Low levels

cause atrophy

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Anterior Pituitary continued

Growth hormone (GH) promotes growth, protein synthesis, & movement of amino acids into cells

Thyroid stimulating hormone (TSH) stimulates thyroid to produce & secrete T4 & T3

Adrenocorticotrophic hormone (ACTH) stimulates adrenal cortex to secrete cortisol, aldosterone

Follicle stimulating hormone (FSH) stimulates growth of ovarian follicles & sperm production

Luteinizing hormone (LH) causes ovulation & secretion of testosterone in testes

Prolactin (PRL) stimulates milk production by mammary glands

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Release of A. Pit. hormones is controlled by hypothalamic releasing & inhibiting factors & by feedback from levels of target gland hormones

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Releasing & inhibiting hormones from hypothalamus are released from axon endings into capillary bed in median eminence Carried by

hypothalamo-hypophyseal portal system directly to another capillary bed in A. Pit. Diffuse into A. Pit.

& regulate secretion of its hormones

Fig 11.15

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Feedback Control of Anterior Pituitary

Involves short feedback loop in which retrograde flow of blood & hormones from A. Pit. to hypothalamus inhibits secretion of releasing hormone

Involves negative feedback of target gland hormones

& during menstrual cycle, estrogen stimulates “LH surge” by positive feedback

Fig 11.17

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Higher Brain Function & Anterior Pituitary Secretion

Hypothalamus receives input from higher brain centers that can affect A. Pit. secretionE.g. psychological stress affects circadian

rhythms, menstrual cycle, & adrenal hormones

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Posterior Pituitary

Stores & releases 2 hormones produced in hypothalamus:Antidiuretic hormone (ADH/vasopressin)

which promotes H20 conservation by kidneysOxytocin which stimulates contractions of

uterus during parturition& contractions of mammary gland alveoli

for milk-ejection reflex

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Hypothalamic Control of Posterior Pituitary

Supraoptic nuclei of hypothalamus produce ADH

Paraventricular nuclei produce oxytocin

Both transported along hypothalamo-hypophyseal tract to posterior pituitary

Release controlled in hypothalamus by neuroendocrine reflexes Fig 11.13

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Adrenal Gland

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Adrenal Glands

Sit on top of kidneys

Each consists of outer cortex & inner medulla2 arise

differently during development

Fig 11.1811-46


Adrenal Glands

Medulla synthesizes & secretes 80% Epi & 20% NEControlled by sympathetic

Cortex is controlled by ACTH & secretes:Cortisol which inhibits glucose utilization &

stimulates gluconeogenesisAldosterone which stimulate kidneys to

reabsorb Na+ and secrete K+

& some supplementary sex steroids

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Adrenal Cortex

Fig 11.19

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Adrenal Medulla

Hormonal effects of Epi last 10X longer than NE Innervated by preganglionic Symp fibers Activated during "fight or flight" response

Causes: Increased respiratory rate Increased HR & cardiac outputGeneral vasoconstriction which increases

venous returnGlycogenolysis & lipolysis

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Stress & the Adrenal Gland

Stress induces a non-specific response called general adaptation syndrome (GAS) Causes ACTH &

cortisol release Often affects

physiology negatively

Fig 11.2011-50

Thyroid Gland

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Thyroid Gland

Is located just below the larynx

Secretes T4 & T3 which set BMR & are needed for growth, development

Fig 11.21

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Thyroid Gland

Consists of microscopic thyroid follicles Outer layer is follicle cells that synthesize T4

Interior filled with colloid, a protein-rich fluid

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Production of Thyroid Hormones

Iodide (I-) in blood is actively transported into follicles & secreted into colloid Where it is oxidized

to iodine (I2) & attached to tyrosines of thyroglobulin A large storage

molecule for T4 & T3

TSH stimulates hydrolysis of T4 & T3s from thyroglobulin & then secretion

Fig 11.2311-54


Diseases of the Thyroid - Goiter

In absence of sufficient dietary iodide, T4 & T3 cannot be made & levels are low Low T4 & T3 don’t

provide negative feedback & TSH levels go up Because TSH is a

trophic hormone, thyroid gland grows

Resulting in a goiter

Fig 11.2511-55


People with inadequate T4 & T3 levels are hypothyroidHave low BMR, weight gain, lethargy, cold

intolerance& myxedema = puffy face, hands, feetDuring fetal development hypothyroidism can

cause cretenism (severe mental retardation)

Diseases of the Thyroid - Hypothyroidism

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Goiters are also produced by Grave's diseaseAutoimmune disease where antibodies act

like TSH & stimulate thyroid gland to grow & oversecrete = hyperthyroidismCharacterized by exopthalmos, weight loss,

heat intolerance, irritability, high BMR

Diseases of the Thyroid - Hyperthyroidism

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Parathyroid Glands

Are 4 glands embedded in lateral lobes of thyroid gland

Secrete Parathyroid hormone (PTH) Most important

hormone for control of blood Ca2+ levels

Fig 11.28

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Parathyroid Hormone

Release stimulated by decreased blood Ca2+

Acts on bones, kidney, & intestines to increase blood Ca2+ levels

Fig 11.29

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Islets of Langerhans

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Islets of Langerhans

Are scattered clusters of endocrine cells in pancreas

Contain alpha & beta cells

Fig 11.30

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Alphas secrete glucagon in response to low blood glucoseStimulates glycogenolysis & lipolysis Increases blood glucose

Islets of Langerhans continued

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Betas secrete insulin in response to low blood glucose Promotes entry of

glucose into cells & conversion of

glucose into glycogen & fat

Decreases blood glucose

Islets of Langerhans continued

Fig 11.31

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Miscellaneous Glands & Hormones

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Pineal Gland

Is located in basal forebrain near thalamus

Secretes melatonin in response to activity of suprachiasmatic nucleus (SCN) of hypothalamus

Fig 11.32

11-66


Pineal Gland continued

SCN is primary timing center for circadian rhythmsReset by daily light/dark changes

Melatonin is involved in aligning physiology with sleep/wake cycle & seasonsSecreted at night & is inhibited by light Inhibits GnRH (antigonadotropic) in many

animals

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Thymus

Is located around trachea below thyroid

Produces T cells of immune system & hormones that stimulate them

Fig 11.3311-68


Sex & Reproductive Hormones

Gonads (testes & ovaries) secrete steroid hormones testosterone, estrogen, & progesterone

Placenta secretes estrogen, progesterone, hCG, and somatomammotropin

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Autocrine & Paracrine Regulation

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Autocrine & Paracrine Regulation

Autocrine regulators are produced & act within same tissue of an organ All autocrines control gene expression in target

cells Paracrine regulators are autocrines that are

produced within one tissue & act on different tissue in same organ.

Autocrines & paracrines include:Cytokines (lymphokines, interleukins)Growth factors (promote growth & cell division) Neutrophins (provides trophic support for

normal & regenerating neurons)

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Prostaglandins (PGs)

Are produced in almost every organ Belong to eicosanoid family -- all derived from

arachidonic acid of plasma membrane

Fig 11.34

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Have wide variety of functionsDifferent PGs may exert antagonistic effects

in tissuesSome promote smooth muscle contraction

& some relaxationSome promote clotting; some inhibit

Promotes inflammatory process of immune system

Plays role in ovulation Inhibits gastric secretion in digestive system

Prostaglandins (PGs) continued

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Cyclooxygenase (COX) 1 & 2 are involved in PG synthesis (Fig 11.34) Are targets of a number of inhibitory non-steroidal

anti-inflammatory drugs (NSAIDs) Aspirin, indomethacin, ibuprofen inhibit both COX

1 & 2 thereby producing side effects Celebrex & Vioxx only inhibit COX 2 & thus have

few side effects

Prostaglandins (PGs) continued

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