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The Pituitary Gland
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MENU
Location & anatomy of the pituitary and hypothalamus
Posterior pituitary hormones
Anterior pituitary hormones
Control of the anterior pituitary
Clinical significance
This tutorial is designed as a single presentation, but if you wish to reviewa particular section, click one of the links below...
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Location of the Pituitary Gland
The pituitary gland controls the
functions of many of the otherendocrine glands.
Click on the pituitary gland to continue..
It is about the size of a pea !.
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Location of the pituitary and hypothalamus
Sella turcica
Anteriorpituitary
Opticchiasm
Mamillarybody
Hypothalamus
Posteriorpituitary
The hypothalamus islocated at the base of thebrain in the posterior part ofthe forebrain (diencephalon).
Pituitary stalkThe pituitary is locatedat the base of the brainwithin a bony cavitycalled the sella turcica.
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Sella turcica
Anteriorpituitary
Opticchiasm
Mamillarybody
Hypothalamus
Posteriorpituitary
Pituitary stalk
The pituitary gland itselfconsists of two main parts:
the anterior lobe(adenohypophysis)
the posterior lobe(neurohypophysis)
Location of the pituitary and hypothalamus
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Anatomy of the hypothalamus and pituitary gland
Anterior
pituitary
Posteriorpituitary
Infundibulum
Neurosecretoryneurones
Hypothalamus
The hypothalamus is theintegration centre for many
physiological processes in thebody
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Anterior
pituitary
Posteriorpituitary
Infundibulum
Neurosecretoryneurones
HypothalamusSupraoptic
nucleus
Paraventricularnucleus
Preopticnucleus
The hypothalamus is theintegration centre for many
physiological processes in thebody.
It is made up of nervoustissue and contains
specialised neuronesarranged in groups callednuclei. These include thepreoptic, the supraopticandthe paraventricularnuclei.
Anatomy of the hypothalamus and pituitary gland
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Anterior
pituitary
Posteriorpituitary
Infundibulum
Neurosecretoryneurones
HypothalamusSupraoptic
nucleus
Paraventricularnucleus
The hypothalamus is theintegration centre for many
physiological processes in thebody.
These nuclei have axons,which terminate in the posteriorlobe of the pituitary.
It is made up of nervoustissue and contains groups
of specialised neuronescalled nuclei. These includethe preoptic, the supraopticand the paraventricularnuclei.
nerve axons
Preopticnucleus
Anatomy of the hypothalamus and pituitary gland
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The anterior lobe islarger than the posteriorlobe and has three parts:
Posteriorpituitary
Infundibulum
Neurosecretoryneurones
HypothalamusSupraoptic
nucleus
Paraventricularnucleus
Anterior
pituitary
the pars distalis(the major part)
the pars tuberalis,
which forms a sleeveround the pituitarystalk
the pars intermedia,which adjoins theposterior lobe
Preopticnucleus
Anatomy of the hypothalamus and pituitary gland
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To understand and remember how the pituitary gland works, it isimportant to understand how the pituitary is formed duringdevelopment.
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The two lobes of the pituitary develop from
different embryological tissues.
The POSTERIOR pituitary is neural tissuederived from primitive ectoderm. It develops as adowngrowth from the hypothalamus.
The ANTERIOR pituitary consists of epithelialtissueand develops upwards as an outgrowth fromthe roof of the mouth.
Development of the pituitary gland
Anteriorlobe
Posteriorlobe
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Development of the pituitary gland
Infundibulum growing downfrom the hypothalamus
Outgrowth of epithelial cellsgrowing up from the roof ofthe mouth
1. Outgrowths of tissue begin to appear from
the hypothalamus and the roof of the mouth
2. The two outgrowthsof tissue start to fusetogether
3. The immature anterior pituitary lobe
separates from the roof of the mouth
roof of mouth
Immature anteriorpituitary gland
4. The anterior and posterior pituitarylobes mature and the bony sellaturcica forms
anteriorlobeposteriorlobe
sella turcica
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In this photograph you can seethe lower part of thehypothalamus connected to theanterior pituitary by the pituitarystalk or infundibulum.
A network of blood capillaries inthe hypothalamus drain into largerportal blood vessels, which linkthe hypothalamus to the anteriorpituitary.
Connections between the hypothalamus and the anteriorpituitary gland
Portal
blood
vessels
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In this photograph you can seethe lower part of thehypothalamus connected to theanterior pituitary by the pituitarystalk or infundibulum.
neurones
Some of the neurones in the hypothalamus terminate close to the bloodcapillaries in the hypothalamus, but there is NO direct neural connection betweenthe hypothalamus and the anterior pituitary gland.
A network of blood capillaries inthe hypothalamus drain into largerportal blood vessels, which linkthe hypothalamus to the anteriorpituitary.
Connections between the hypothalamus and the anteriorpituitary gland
Portal
blood
vessels
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You have now seen:
1. The anatomical structure of the pituitary gland
Lets now look at the posterior pituitary gland in moredetail.
2. Its spatial and anatomical relationship with the hypothalamus
3. How each pituitary lobe develops embryologically
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Posterior Pituitary Hormones
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Control of the posterior pituitary gland
Axons of hypothalamic-hypophyseal tract
Infundibulum
Anteriorpituitary
pituitary vein
Hypothalamus
Anteriorpituitary
Oxytocin
ADH
The posterior pituitary secretes2 important hormones :
Posterior pituitary
Anti-diuretic hormone (ADH),also called vasopressin
Oxytocin
kidney
breast and uterus
C l f h i i i l d
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Axons of hypothalamic-hypophyseal tract
Infundibulum
Supraopticnucleus
Paraventricularnucleus
Anteriorpituitary
pituitary vein
Hypothalamus
Anteriorpituitary
Oxytocin
ADH
Both hormones are peptides,which are synthesised in the cell
bodies of neurones in theparaventricularand supraopticnuclei of the hypothalamus.
Control of the posterior pituitary gland
C t l f th t i it it l d
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Infundibulum
Anteriorpituitary
pituitary vein
Hypothalamus
Anteriorpituitary
Oxytocin
ADH
Axons of hypothalamic-hypophyseal tract
The hormones travel from thehypothalamus to the posterior
pituitary via axons in the pituitarystalk. This neuronal connection iscalled the hypothalamic-hypophysealtract.
Supraopticnucleus
Paraventricularnucleus
Control of the posterior pituitary gland
C t l f th t i it it l d
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Infundibulum
Anteriorpituitary
pituitary vein
Hypothalamus
Anteriorpituitary
Oxytocin
ADH
Axons of hypothalamic-hypophyseal tract
The hormones are stored in theaxon terminals in the posterior
pituitary and can be secretedinto the bloodstream when nerveimpulses travel down theneurones
Supraopticnucleus
Paraventricularnucleus
Control of the posterior pituitary gland
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What are the actions of the posterior pituitary hormones?
ADH increases waterreabsorption in the kidney andso modulates blood pressure
A deficiency in ADH causesdiabetes insipidus (polyuria,hypotension)
Anti-diuretic hormone (ADH)(vasopressin)
ADH
External stimuluse.g. low bloodpressure
Posteriorpituitary
ADH secretion is stimulated
by low blood pressure
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Oxytocin secretion isstimulated by stretching of thecervix during birth and sucklingof the baby at the breast
A deficiency of oxytocin causesa failure to progress in labourand difficulty with breast feeding
Oxytocin
Oxytocin
External stimuluse.g. stretching of
cervix or suckling
Oxytocin stimulates uterinecontractions during labour andthe milk ejection reflex after birth
Posteriorpituitary
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Now lets look at the anterior pituitary gland:
1. The cellular structure of the anterior pituitary gland.
2. What hormones does it secrete?
3. What are the effects of these hormones?
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Anterior Pituitary Hormones
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Cellular structure of the anterior pituitary gland
Somatotrophsproduce
growth hormone (GH)
ANTERIOR
PITUITARYsinusoid
The anterior pituitary is composed of groups of
epithelial cells surrounded by wide capillaries calledsinusoids.
Different populations of cells produce differenthormones.
For example:
GH
GH
GH
GH
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ANTERIOR
PITUITARYsinusoid
The anterior pituitary is composed of groups of
epithelial cells surrounded by wide capillaries calledsinusoids.
Different populations of cells produce differenthormones.
PRL
PRL
PRL
PRL
Lactotrophsproduce prolactin (PRL)
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ANTERIOR
PITUITARYsinusoid
The anterior pituitary is composed of groups of
epithelial cells surrounded by wide capillaries calledsinusoids.
Different populations of cells produce differenthormones.
TSH
TSH
TSH
TSH
Thyrotrophsproduce thyroid-stimulating hormone (TSH)
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ANTERIOR
PITUITARYsinusoid
The anterior pituitary is composed of groups of
epithelial cells surrounded by wide capillaries calledsinusoids.
Different populations of cells produce differenthormones.
Corticotrophsproduce bothadrenocorticotrophic hormone (ACTH) andmelanocyte-stimulating hormone (MSH)
MSHACTH
ACTH
MSH
MSH
ACTH
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ANTERIOR
PITUITARYsinusoid
The anterior pituitary is composed of groups of
epithelial cells surrounded by wide capillaries calledsinusoids.
Different populations of cells produce differenthormones.
LH
FSH
FSH
LH
FSH
Gonadotrophsproduce luteinising hormone (LH)and follicle-stimulating hormone (FSH)
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The following screens give a brief summary of what the anterior pituitaryhormones do.
Each hormone may be dealt with in more detail in other presentations.
Anterior pituitary hormones Growth Hormone
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1.Growth Hormone(GH) regulates growth
in the muscles and bones and opposes theaction of insulin
Somatotrophs in the anterior pituitarygland secrete GH
GH
Anterior pituitary hormones - Growth Hormone
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1.Growth Hormone(GH) regulates growth
in the muscles and bones and opposes theaction of insulin
Somatotrophs in the anterior pituitarygland secrete GH
GH
Many body cells (chondrocytes, fat cells,muscle, but mainly the liver) respond to GHby secreting insulin-like growth factor (IGF)
+
IGF
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1.Growth Hormone(GH) regulates growth
in the muscles and bones and opposes theaction of insulin
Somatotrophs in the anterior pituitarygland secrete GH
GH
Many body cells (chondrocytes, fat cells,muscle, but mainly the liver) respond to GHby secreting insulin-like growth factor (IGF)
+
IGF
Growth and cellular differentiationin bone, muscle and adipose cells
Therefore, GH acts indirectly via IGF toregulate body growth
Anterior pituitary hormones - LH and FSH
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2.Luteinising Hormone (LH)andFollicle Stimulating Hormone (FSH)
control both the ovaries and testes
Gonadotrophs in the anterior pituitary glandsecrete LH and FSH
LH FSH
p y
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ovary
2.Luteinising Hormone (LH)andFollicle Stimulating Hormone (FSH)
control both the ovaries and testes
Gonadotrophs in the anterior pituitary glandsecrete LH and FSH
In the female, LH and FSH stimulate
the ovary.
LH FSH
oestrogen progesterone
inhibin
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2.Luteinising Hormone (LH)andFollicle Stimulating Hormone (FSH)
control both the ovaries and testes
Gonadotrophs in the anterior pituitary glandsecrete LH and FSH
In the female, LH and FSH stimulate
the ovary.
The ovarian steroid hormones (oestradioland progesterone) have effects on many
other parts of the body (bone, brain,vascular tissue etc.), secondary sexualcharacteristics and behaviour.
LH FSH
Effects on bone, brain, vascular tissue etc.,behaviour
oestrogen progesterone
inhibin ovary
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2.Luteinising Hormone (LH)andFollicle Stimulating Hormone (FSH)
control both the ovaries and testes
Gonadotrophs in the anterior pituitary glandsecrete LH and FSH
FSHLH
testosteroneinhibin
testis
In the male, LH and FSH stimulatethe Leydig cells and the Sertoli cellsin the testis, respectively, to secretetestosterone and inhibin
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2.Luteinising Hormone (LH)andFollicle Stimulating Hormone (FSH)
control both the ovaries and testes
Gonadotrophs in the anterior pituitary glandsecrete LH and FSH
FSHLH
testosterone
Spermatogenesis, secondary sexualcharacteristics and behaviour
inhibin
testis
In the male, LH and FSH stimulatethe Leydig cells and the Sertoli cellsin the testis, respectively, to secretetestosterone and inhibin
Anterior pituitary hormones - Prolactin
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3.Prolactin (PRL) initiates lactation andpromotes the growth of the mammaryglands, ovaries and testes
Lactotrophs in the anterior pituitary glandsecrete PRL PRL
Anterior pituitary hormones Prolactin
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3.Prolactin (PRL) initiates lactation andpromotes the growth of the mammaryglands, ovaries and testes
Lactotrophs in the anterior pituitary glandsecrete PRL PRL
Prolactin acts directly on the breast tostimulate milk production.
breast
Milkproduction
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3.Prolactin (PRL) initiates lactation andpromotes the growth of the mammary
glands, ovaries and testes
Lactotrophs in the anterior pituitary glandsecrete PRL PRL
Prolactin acts directly on the breast tostimulate milk production.
Growth of mammary glands,ovaries and testes
breast
Milkproduction
Anterior pituitary hormones - Thyroid-stimulating hormone
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4.Thyroid-stimulating hormone (TSH)regulates the thyroid gland
Thyrotrophs in the anterior pituitary glandsecrete TSH
TSH
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4.Thyroid-stimulating hormone(TSH) regulates the thyroid gland
Thyrotrophs in the anterior pituitary glandsecrete TSH
TSHTSH acts on the thyroid gland to stimulate the
release of thyroid hormones (Thyroxine, T4,Tri-iodothyronine, T3.
thyroid
parathyroids
Thyroid hormones
Anterior pituitary hormones - Thyroid-stimulating hormone
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4.Thyroid-stimulating hormone (TSH)regulates the thyroid gland
Thyrotrophs in the anterior pituitarygland secrete TSH
TSH
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4.Thyroid-stimulating hormone (TSH)regulates the thyroid gland
Thyrotrophs in the anterior pituitarygland secrete TSH
TSHTSH acts on the thyroid gland to stimulate the
release of thyroid hormones (Thyroxine, T4,Tri-iodothyronine, T3, and Calcitonin) as wellas changes to the thyroid gland
thyroid
parathyroids
Thyroid hormones
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4.Thyroid-stimulating hormone (TSH)regulates the thyroid gland
Thyrotrophs in the anterior pituitarygland secrete TSH
TSHTSH acts on the thyroid gland to stimulate the
release of thyroid hormones (Thyroxine, T4,Tri-iodothyronine, T3.
Metabolism, heat production,growth.
The thyroid hormones play an important role incontrolling control carbohydrate and fatmetabolism, and basal metabolic rate.
thyroid
parathyroids
Thyroid hormones
Anterior pituitary hormones - Adrenocorticotrophic hormone
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5.Adrenocorticotrophic hormone(ACTH) controls hormone secretion from
the adrenal cortex
Corticotrophs in the anterior pituitarygland secrete ACTH
ACTH
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5.Adrenocorticotrophic hormone(ACTH) controls hormone secretion from
the adrenal cortex
Corticotrophs in the anterior pituitarygland secrete ACTH
ACTHACTH acts on the adrenal cortex to stimulate therelease of glucocorticoids (mainly cortisol) and
adrenal androgens (mainly androstenedione anddehydroepiandrosterone (DHEA))
Adrenal cortex hormones
adrenalcortex
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5.Adrenocorticotrophic hormone(ACTH) controls hormone secretion from
the adrenal cortex
Corticotrophs in the anterior pituitarygland secrete ACTH
ACTHACTH acts on the adrenal cortex to stimulate therelease of glucocorticoids (mainly cortisol) and
adrenal androgens (mainly androstenedione anddehydroepiandrosterone (DHEA))
Metabolism, immune system, stressresponses, testosterone and oestrogen
Adrenal cortex hormones
adrenalcortex
Cortisol controls the metabolism of carbohydrates,fats and proteins, inflammatory and immuneresponses, and responses to stress
Anterior pituitary hormones - Melanocyte-stimulating hormone
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6.Melanocyte Stimulating Hormone (MSH)stimulates melanocytes in the skin
Corticotrophs in the anterior pituitary glandalso secrete MSH
MSH
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6.Melanocyte Stimulating Hormone (MSH)stimulates melanocytes in the skin
Corticotrophs in the anterior pituitary glandsecrete MSH
MSH
MSH acts on melanocytes in the epidermis ofthe skin to stimulate the secretion of melanin
Melanin
melanocytesin the skin
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6.Melanocyte Stimulating Hormone (MSH)stimulates melanocytes in the skin
Corticotrophs in the anterior pituitary glandsecrete MSH
MSH
MSH acts on melanocytes in the epidermis ofthe skin to stimulate the secretion of melanin
Skin pigmentation
MelaninMelanin controls pigmentation in the skin
melanocytesin the skin
Summary of hormones secreted by the anterior pituitary gland
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Adrenocorticotrophic Hormone (ACTH) controls hormone secretion from the adrenal cortex
Growth Hormone(GH) regulates growth in muscles and bones and opposes the action of insulin
Prolactin initiates lactation and promotes the growth of the mammary glands, ovaries and testes
Thyroid Stimulating Hormone (TSH) regulates the thyroid gland
So the anterior pituitary secretes at least 7 important hormones:
Melanocyte Stimulating Hormone (MSH)stimulates melanocytes in the skin
Luteinising Hormone (LH) and
Follicle Stimulating Hormone (FSH)
control both the ovaries and the testes
Essentials in
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Biomedical Science
Kings College London
Date last modified:26/09/2001Stuart Milligan
Victoria Pocock
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Control of the Anterior Pituitary
B t h t t l th diff ti l ti f th t i it it
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But what controls the differential secretion of the anterior pituitarygland hormones?
The following screens will show:
1. How the hypothalamus controls the anterior pituitary gland
2. The importance of negative feedback control of the hypothalamic-pituitaryaxis.
Hypothalamic control of the anterior pituitary hormones
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These hypothalamicneurones releaseneurosecretoryhormones into theportal blood vessels
We have already seen thatmany neurones terminate inthe base of the hypothalamusin close association with theportal blood vessels.
hypothalamic
neuronesHypothalamus
Anterior
pituitary
NEUROSECRETORYHORMONES
portal bloodvessels
The hypothalamic hormonescontrol the release of anteriorpituitary hormones
Hypothalamic control of the anterior pituitary hormones
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Hypothalamic control of the anterior pituitary hormones
Let us look at how thehypothalamic hormonescontrol the release of anteriorpituitary hormones using
thyroid stimulating hormone(TSH)as an example..
In the cold, specificneurones in thehypothalamus secrete the neurosecretory
Only certain neurones in thehypothalamus can secreteTRH Other hypothalamic
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hypothalamicneurones
Hypothalamus
hormone Thyrotrophin Releasing Hormone(TRH)
Anterior
pituitary
TRH
Lowtemperature
+
TRH. Other hypothalamicneurones secrete differentneurosecretory hormonesunder different conditions.
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hypothalamicneurones
Hypothalamus
TRHstimulates thethyrotrophs in theanterior pituitary to
secrete thyroidstimulatinghormone (TSH)Anterior
pituitary
TRH
Lowtemperature
+
TSH then stimulates the thyroid to releasethyroid hormones, which subsequentlycause an increase in body temperature
thyrotrophsTSH
Thyroid
Thyroidhormones
Increased body
temperature
Hypothalamic hormones that control the anterior pituitary
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Growth Hormone Releasing Hormone (GHRH)
Somatostatin
The hypothalamus secretes several hormones that control thesecretion of anterior pituitary hormones:
GH+
Hypothalamic hormones that control the anterior pituitary
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Growth Hormone Releasing Hormone (GHRH)
Somatostatin
The hypothalamus secretes several hormones that control thesecretion of anterior pituitary hormones:
Corticotrophin Releasing Hormone (CRH) + ACTH
Hypothalamic hormones that control the anterior pituitary
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Growth Hormone Releasing Hormone (GHRH)
Somatostatin
The hypothalamus secretes several hormones that control thesecretion of anterior pituitary hormones:
Corticotrophin Releasing Hormone (CRH)
Gonadotrophin Releasing Hormone (GnRH) LHFSH
+
Hypothalamic hormones that control the anterior pituitary
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Growth Hormone Releasing Hormone (GHRH)
Somatostatin
Thyrotrophin Releasing Hormone (TRH)
The hypothalamus secretes several hormones that control thesecretion of anterior pituitary hormones:
Corticotrophin Releasing Hormone (CRH)
Gonadotrophin Releasing Hormone (GnRH)
TSH+
Hypothalamic hormones that control the anterior pituitary
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Growth Hormone Releasing Hormone (GHRH)
Somatostatin
Dopamine
Thyrotrophin Releasing Hormone (TRH)
Prolactin Releasing Factors (PRF),one of which is TRH
The hypothalamus secretes several hormones that control thesecretion of anterior pituitary hormones:
Corticotrophin Releasing Hormone (CRH)
Gonadotrophin Releasing Hormone (GnRH)
-PRL
+
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The hypothalamic hormones are the
primary hormones controlling thesecretion of the anterior pituitaryhormones.
However, many other factors feed intothe control of the hypothalamic-pituitary
axis..
Lets look at some of these ..
Specific stimuli
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Hypothalamus
Pituitary
We have already seen that specificstimuli (e.g. cold in the case ofTSH) feed into the hypothalamiccontrol system
Specific stimuliCircadian changes
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Hypothalamus
Pituitary
SLEEP
GH levels
24 hrs
In addition, many hormones showdaily rhythms.
Note that GH is released in pulsesduring the hours of sleep.
Specific stimuliCircadian changes
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Pituitary
Pulse generator
Pulses of GnRH
LH levels
24 hrs
The secretion of GnRH seemsto be governed by a
hypothalamic pulse generator.
24 hour profile of LH levels in ayoung adult.
Note the pulses of LH markedby arrows.
Specific stimuliCircadian changes
Pulses?
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Hypothalamus
Pituitary
Feedback from peripheral signals
(usually negative feedback)e.g. thyroid hormones, gonadal steroids
And a very important control formost the the anterior pituitaryhormones is feedback control.
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Lets use TSH as an example for looking at
feedback control.
Negative feedback controls of the hypothalamic-pituitary axis
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Specific external signals,e.g. low temperature,stimulate the secretion ofTRH by the
hypothalamus.
+hypothalamicneurones
Hypothalamus
Anteriorpituitary
TRH
Lowtemperature
thyrotrophsTSH
TRH stimulates thesecretion of TSH by theanterior pituitary.
Negative feedback controls of the hypothalamic-pituitary axis
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TSH stimulates thethyroid to releasethe thyroidhormones, T3 andT4.
+hypothalamicneurones
Hypothalamus
Anteriorpituitary
TRH
Lowtemperature
thyrotrophsTSH
Thyroid
T4
T3
Negative feedback controls of the hypothalamic-pituitary axis
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The thyroid hormonesfeedback onto thehypothalamus and theanterior pituitary tosuppress further TSHproduction. This is anegative feedback effect.
hypothalamicneurones
Hypothalamus
Anteriorpituitary
TRH
thyrotrophsTSH
Thyroid
T4
T3
Negative feedback controls of the hypothalamic-pituitary axis
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So high levels ofthyroid hormonessuppress TRH andTSH secretion.
hypothalamicneurones
Hypothalamus
Anteriorpituitary
thyrotrophs
Thyroid
T4
T3
(TRH)
(TSH)
Negative feedback controls of the hypothalamic-pituitary axis
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However, when there arelow levels of thyroidhormones, TRH andTSH secretion will be
high.
hypothalamicneurones
Hypothalamus
Anteriorpituitary
TRH
thyrotrophsTSH
Thyroid
T4
T3
Essentials in
Biomedical Science
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Biomedical Science
Kings College LondonDate last modified:
26/09/2001Stuart Milligan
Victoria Pocock
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Clinical significance
Because the control of the hypothalamic-pituitary axis involves a number of steps
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pituitary axis involves a number of steps,problems of under-secretion or over-
secretion of hormones can arise fromdifferent physiological defects in thecontrol pathway.
Using growth hormone (GH) as anexample, we will now look now howproblems might arise.
But first a reminder of the controls of GH...
Control of Growth Hormone
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hypothalamicneurones
Hypothalamus
somatotrophsAnteriorpituitary
Liver
SomatostatinGHRH
+
GH
GHRH stimulatessecretion of GH bythe anterior pituitary
GH stimulates secretionof insulin-like growth
factors (IGF) by theliver.
IGFs stimulate growthin bones, muscles andfat IGF
Whereassomatostatininhibits GHsecretion
Control of GH secretionBlood glucose
ExerciseSleep
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But other factors such assleep, exercise, stress,
food intake and bloodsugar levels also influencethe release of thesehormones
Hypothalamus
Pituitary
GH
Liver
IGF-1
FoodStress
SomatostatinGHRH +
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Given the understanding of the normal control of GH, well now
look at how it can go wrong..
Hypothalamus
Hypersecretion of GH
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Pituitary
GH
Liver
IGF-1
In a few people, the pituitary continues tosecrete GH independently of the normal
regulatory mechanisms.
The levels of GH increase above normal,leading to excess bone growth and organenlargement.
The hypersecretion of GH alsocauses changes in sugar and lipidmetabolism and can cause diabetes.
Excess bone growth
Organ enlargement
Diabetes
GHRH + Somatostatin
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Understanding how the system
works also gives us an insightinto where the controlmechanisms can break down
Lets look at a growth disorders
such as short stature as an
example.
HypothalamusWhat could cause short stature?
Problems can occur in the hypothalamuse.g. defects in GHRH production
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Pituitary
GH
Liver
GHRH
+Somatostatin
IGF-1
e g de ects G p oduct o
Problems can occur in the pituitarye.g. defects in GH secretion or bioactivity
Problems can occur in the abilityof cells to produce IGF.
Problems can occur in the target organse.g. defects in growth response
So there is a
complex,
hierarchical
control system and problems
can occur at any
of the levels
Lets now look at how the function of
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hypothalamic-pituitary axis be tested...
These tests are often calledChallenge testsbecause they aredesigned to challenge the normaloperation of the system..
1. Hypothalamic releasing factors, e.g. TRHand GnRH, are useful to identifyspecific functional cell types in the anterior pituitary (thyrotrophs and
d h ) b hi b d f di i f h i i i
Challenge Tests
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gonadotrophs), but this test cannot be used for diagnosis of hypopituitarism orhyperpituitarism.
Time (minutes)
0 20 60 90-15
2
4
6
8
FSH mU/L
GnRH200 g IV
20
Time (minutes)
0 20 60 90-15
10
LH U/L
GnRH200 g IV
Note the rapid FSH response when
GnRH is given to normal subjects
And the same dose of GnRHresults in similar rapid rises in LH
2. Synthetic drugs can be given to investigate whether the negative feedback controlof the anterior pituitary is working properly ( e.g. dexamethasone(suppresses ACTH)and metyrapone (blocks cortisol secretion))
Challenge Tests
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Plasma ACTH = 2 pmol/L
and metyrapone(blocks cortisol secretion))
Cortisol
ACTH
-
Normal negative feedback
control of ACTH by cortisolsecreted by the adrenal cortex
Cortisol
-
ACTH
Metyrapone
Metyrapone blocks cortisol
secretion from the adrenalcortex
Plasma ACTH = 10 pmol/L
Cortisol
-
ACTH
DEX
Dexamethasone suppresses
ACTH secretion by the anteriorpituitary
Plasma ACTH = 37 pmol/L+
Note the increased level of ACTH due toblockage of cortisol secretion and thereforeremoval of negative feedback control
Note the reduced level of ACTHdue to suppression bydexamethasone
3. The use of a physiological stimulus,e.g. insulin-induced hypoglycaemia,(insulin tolerance test) can be used to
Challenge Tests
HypopituitaryNormal
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( )help define defects in the system
For example, in normal patients,insulin-induced hypoglycaemiaactivates hypothalamic neuronesto stimulate pituitary secretion of
corticotrophin, GH and prolactin.
But, in subjects with hypopituitarism,plasma cortisol and and serum GH
levels are far below normal levels.
0 30 60 90 12
Time (minutes)
Insulin
0.15 U/kg
Hypopituitary
5
3
1
800
600
400
200
20
10
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Understanding the normal control of thehypothalamic-pituitary axis allows the system tobe manipulated to achieve different aims
Lets use the control of reproduction by GnRH,LH, FSH and ovarian hormones as anexample..
Control ofreproduction
Hypothalamus
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The basic operation of the
hypothalamic-pituitary-gonadalsystem is shown opposite.
Understanding this system allowed formsof contraception to be developed ..
Pituitary
LHFSH
Ovary
Oestradiol
GnRH
+
+GnRH drives FSH productionfrom the pituitary, and FSHstimulates follicle growth.
Oestradiol produced by thefollicle provides negativefeedback.
Control ofreproduction
Hypothalamus
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The negative feedback control
of oestrogens was the originalbasis of the oral contraceptivepill
Pituitary
LHFSH
Ovary
GnRH
High doses of oestrogens act onthe hypothalamic-pituitary axis tosuppress LH and FSH secretionand so suppress follicle growthand prevent ovulation
Oestradiol
Oral oestrogens
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But we can also use our
understanding to stimulate
reproduction
Stimulation ofovarian function
HypothalamusI t t t f i f tilit it i
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One method is give pulses ofGnRH: these will stimulate thepituitary to secrete more LH andFSH.
GnRH
Pituitary
LHFSH
Ovary
(pulses)
In some treatments for infertility, it isnecessary to stimulate the ovaries
Growth of more follicles
Oestradiol
Stimulation offollicular growth
Hypothalamus
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Or: an alternative is togive FSH to stimulate theovary directly
GnRH
Pituitary
FSH
Ovary
Growth of more follicles
Oestradiol
Hypothalamus
Stimulation offollicular growth
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Pituitary
LHFSH
Ovary
Oestradiol
GnRH
Or another wayis to give an anti-
oestrogen (e.g. clomiphene). Theanti-oestrogen blocks the negativefeedback of oestradiol, sogonadotrophin levels rise!
Clomiphene
Therefore, clomiphene is often used
as a fertility treatment for women toincrease the number of folliclesgrowing and ovulating
Growth of more follicles
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