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This tutorial is designed as a single presentation, but if you wish to review a particular section, click one of the links below... Location & anatomy of the pituitary and hypothalamus Posterior pituitary hormones Anterior pituitary hormones Control of the anterior pituitary
Clinical significance
Lets now look at the anatomy of the pituitary gland and its relationship to the hypothalamus and surrounding tissues
Hypothalamus
Mamillary body
Pituitary stalk
The pituitary is located at the base of the brain within a bony cavity called the sella turcica.
Posterior pituitary
Sella turcica
Hypothalamus
Mamillary body
Pituitary stalk
The pituitary gland itself consists of two main parts: the anterior lobe (adenohypophysis)
Posterior pituitary
Sella turcica
Infundibulum
Neurosecretory neurones
Anterior pituitary
Posterior pituitary
Hypothalamus
Infundibulum
Neurosecretory neurones
Anterior pituitary
Posterior pituitary
Hypothalamus
Infundibulum
Neurosecretory neurones
nerve axons
Anterior pituitary
Posterior pituitary
The anterior lobe is larger than the posterior lobe and has three parts: the pars tuberalis, which forms a sleeve round the pituitary stalk the pars distalis (the major part) the pars intermedia, which adjoins the posterior lobe
Hypothalamus
Neurosecretory neurones
Infundibulum
Anterior pituitary
Posterior pituitary
To understand and remember how the pituitary gland works, it is important to understand how the pituitary is formed during development.
The two lobes of the pituitary develop from different embryological tissues.
Anterior lobe Posterior lobe
The POSTERIOR pituitary is neural tissue derived from primitive ectoderm. It develops as a downgrowth from the hypothalamus. The ANTERIOR pituitary consists of epithelial tissue and develops upwards as an outgrowth from the roof of the mouth.
4. The anterior and posterior pituitary lobes mature and the bony sella turcica forms 2. The two outgrowths of tissue start to fuse together
posterior lobe
In this photograph you can see the lower part of the hypothalamus connected to the pituitary gland by the pituitary stalk or infundibulum.
Hypothalamus
Pituitary stalk
Pituitary
In this photograph you can see the lower part of the hypothalamus connected to the anterior pituitary by the pituitary stalk or infundibulum.
A network of blood capillaries in the hypothalamus drain into larger portal blood vessels, which link the hypothalamus to the anterior pituitary.
In this photograph you can see the lower part of the hypothalamus connected to the anterior pituitary by the pituitary stalk or infundibulum.
neurones
A network of blood capillaries in the hypothalamus drain into larger portal blood vessels, which link the hypothalamus to the anterior pituitary.
Some of the neurones in the hypothalamus terminate close to the blood capillaries in the hypothalamus, but there is NO direct neural connection between the hypothalamus and the anterior pituitary gland.
You have now seen: 1. The anatomical structure of the pituitary gland 2. Its spatial and anatomical relationship with the hypothalamus
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The posterior pituitary secretes 2 important hormones : Anti-diuretic hormone (ADH), also called vasopressin
Infundibulum
Oxytocin
Posterior pituitary
ADH
Anterior Anterior pituitary pituitary
kidney
pituitary vein
Oxytocin
Both hormones are peptides, which are synthesised in the cell bodies of neurones in the paraventricular and supraoptic nuclei of the hypothalamus.
Infundibulum
ADH
Anterior Anterior pituitary pituitary
pituitary vein
Oxytocin
The hormones travel from the hypothalamus to the posterior pituitary via axons in the pituitary stalk. This neuronal connection is called the hypothalamichypophyseal tract.
Infundibulum
ADH
Anterior Anterior pituitary pituitary
pituitary vein
Oxytocin
Infundibulum
The hormones are stored in the axon terminals in the posterior pituitary and can be secreted into the bloodstream when nerve impulses travel down the neurones
ADH
Anterior Anterior pituitary pituitary
pituitary vein
Oxytocin
Posterior pituitary
ADH
Oxytocin
Oxytocin secretion is stimulated by stretching of the cervix during birth and suckling of the baby at the breast Oxytocin stimulates uterine contractions during labour and the milk ejection reflex after birth
Posterior pituitary
A deficiency of oxytocin causes a failure to progress in labour and difficulty with breast feeding
Oxytocin
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GH
sinusoid
GH
ANTERIOR PITUITARY
GH
The anterior pituitary is composed of groups of epithelial cells surrounded by wide capillaries called sinusoids. Different populations of cells produce different hormones. PRL
PRL
PRL
sinusoid
The anterior pituitary is composed of groups of epithelial cells surrounded by wide capillaries called TSH sinusoids. Different populations of cells produce different hormones.
TSH
ANTERIOR PITUITARY
sinusoid
TSH
The anterior pituitary is composed of groups of epithelial cells surrounded by wide capillaries called sinusoids. Different populations of cells produce different hormones.
MSH ACTH
MSH
sinusoid
MSH Corticotrophs produce both adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH)
The anterior pituitary is composed of groups of epithelial cells surrounded by wide capillaries called sinusoids. LH Different populations of cells produce different hormones. FSH
FSH
sinusoid
LH FSH
ANTERIOR PITUITARY
The following screens give a brief summary of what the anterior pituitary hormones do. Each hormone may be dealt with in more detail in other presentations.
1. Growth Hormone (GH) regulates growth in the muscles and bones and opposes the action of insulin
Somatotrophs in the anterior pituitary gland secrete GH
GH
1. Growth Hormone (GH) regulates growth in the muscles and bones and opposes the action of insulin
Somatotrophs in the anterior pituitary gland secrete GH Many body cells (chondrocytes, fat cells, muscle, but mainly the liver) respond to GH by secreting insulin-like growth factor (IGF)
IGF
GH
1. Growth Hormone (GH) regulates growth in the muscles and bones and opposes the action of insulin
Somatotrophs in the anterior pituitary gland secrete GH Many body cells (chondrocytes, fat cells, muscle, but mainly the liver) respond to GH by secreting insulin-like growth factor (IGF)
IGF
GH
Therefore, GH acts indirectly via IGF to regulate body growth Growth and cellular differentiation in bone, muscle and adipose cells
2. Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) control both the ovaries and testes
Gonadotrophs in the anterior pituitary gland secrete LH and FSH
LH In the female, LH and FSH stimulate the ovary. FSH
inhibin
ovary
oestrogen
progesterone
2. Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) control both the ovaries and testes
Gonadotrophs in the anterior pituitary gland secrete LH and FSH
LH In the female, LH and FSH stimulate the ovary. FSH
inhibin The ovarian steroid hormones (oestradiol and progesterone) have effects on many other parts of the body (bone, brain, vascular tissue etc.), secondary sexual characteristics and behaviour.
ovary
oestrogen
progesterone
2. Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) control both the ovaries and testes
Gonadotrophs in the anterior pituitary gland secrete LH and FSH LH In the male, LH and FSH stimulate the Leydig cells and the Sertoli cells in the testis, respectively, to secrete testosterone and inhibin
testosterone
FSH
inhibin
testis
2. Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) control both the ovaries and testes
Gonadotrophs in the anterior pituitary gland secrete LH and FSH LH In the male, LH and FSH stimulate the Leydig cells and the Sertoli cells in the testis, respectively, to secrete testosterone and inhibin
testosterone
FSH
inhibin
testis
PRL
3. Prolactin (PRL) initiates lactation and promotes the growth of the mammary glands, ovaries and testes
PRL
3. Prolactin (PRL) initiates lactation and promotes the growth of the mammary glands, ovaries and testes
PRL
thyroid
Thyroid hormones
parathyroids
thyroid
Thyroid hormones
thyroid
The thyroid hormones play an important role in controlling control carbohydrate and fat metabolism, and basal metabolic rate.
5. Adrenocorticotrophic hormone (ACTH) controls hormone secretion from the adrenal cortex
Corticotrophs in the anterior pituitary gland secrete ACTH
ACTH acts on the adrenal cortex to stimulate the release of glucocorticoids (mainly cortisol) and adrenal androgens (mainly androstenedione and dehydroepiandrosterone (DHEA)) ACTH
adrenal cortex
5. Adrenocorticotrophic hormone (ACTH) controls hormone secretion from the adrenal cortex
Corticotrophs in the anterior pituitary gland secrete ACTH
ACTH acts on the adrenal cortex to stimulate the release of glucocorticoids (mainly cortisol) and adrenal androgens (mainly androstenedione and dehydroepiandrosterone (DHEA))
Cortisol controls the metabolism of carbohydrates, fats and proteins, inflammatory and immune responses, and responses to stress
ACTH
adrenal cortex
Melanin
Melanin
Skin pigmentation
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Kings College London Date last modified: 26/09/2001 Stuart Milligan Victoria Pocock
But what controls the differential secretion of the anterior pituitary gland hormones?
Hypothalamus
These hypothalamic neurones release neurosecretory hormones into the portal blood vessels
portal blood vessels
hypothalamic neurones
NEUROSECRETORY HORMONES
Anterior pituitary
Let us look at how the hypothalamic hormones control the release of anterior pituitary hormones using thyroid stimulating hormone (TSH) as an example..
In the cold, specific neurones in the hypothalamus secrete the neurosecretory hormone Thyrotrophin Releasing Hormone (TRH)
Only certain neurones in the hypothalamus can secrete TRH. Other hypothalamic neurones secrete different neurosecretory hormones under different conditions.
+
Low temperature Hypothalamus hypothalamic neurones
TRH
Anterior pituitary
+
Low temperature Hypothalamus hypothalamic neurones
TRH
TSH
thyrotrophs
Anterior pituitary
Thyroid hormones Thyroid
TRH stimulates the thyrotrophs in the anterior pituitary to secrete thyroid stimulating hormone (TSH)
TSH then stimulates the thyroid to release thyroid hormones, which subsequently cause an increase in body temperature
GH
ACTH
LH FSH
TSH
PRL
The hypothalamic hormones are the primary hormones controlling the secretion of the anterior pituitary hormones. However, many other factors feed into the control of the hypothalamic-pituitary axis.. Lets look at some of these ..
Specific stimuli
We have already seen that specific stimuli (e.g. cold in the case of TSH) feed into the hypothalamic control system
Hypothalamus
Pituitary
Hypothalamus
Pituitary
GH levels
SLEEP 24 hrs
LH levels
Pituitary
24 hrs
Hypothalamus
And a very important control for most the the anterior pituitary hormones is feedback control .
Pituitary
Feedback from peripheral signals (usually negative feedback) e.g. thyroid hormones, gonadal steroids
Low temperature
+
Specific external signals, e.g. low temperature, stimulate the secretion of TRH by the hypothalamus.
Hypothalamus
hypothalamic neurones
TRH
TSH
Anterior pituitary
thyrotrophs
Low temperature
TSH stimulates the thyroid to release the thyroid hormones, T3 and T4.
+
Hypothalamus hypothalamic neurones
TRH
TSH
T4 T3 Thyroid
Anterior pituitary
thyrotrophs
The thyroid hormones feedback onto the hypothalamus and the anterior pituitary to suppress further TSH production. This is a negative feedback effect.
Hypothalamus
hypothalamic neurones
TRH
TSH
Anterior pituitary
Thyroid
thyrotrophs
T4 T3
Hypothalamus
(TSH)
T4 T3 Thyroid
Anterior pituitary
thyrotrophs
However, when there are low levels of thyroid hormones, TRH and TSH secretion will be high.
Hypothalamus
hypothalamic neurones
TRH
TSH
Anterior pituitary
Thyroid
thyrotrophs
T4 T3
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Kings College London Date last modified: 26/09/2001 Stuart Milligan Victoria Pocock
Because the control of the hypothalamicpituitary axis involves a number of steps, problems of under-secretion or oversecretion of hormones can arise from different physiological defects in the control pathway. Using growth hormone (GH) as an example, we will now look now how problems might arise. But first a reminder of the controls of GH...
Hypothalamus
GHRH stimulates secretion of GH by the anterior pituitary
GHRH
+
somatotrophs
Anterior pituitary
GH
IGFs stimulate growth in bones, muscles and fat
IGF
Liver
Control of GH secretion
But other factors such as sleep, exercise, stress, food intake and blood sugar levels also influence the release of these hormones
Blood glucose
Exercise
Stress
Sleep
Hypothalamus
Food
GHRH
Somatostatin
Pituitary
GH IGF-1
Liver
Given the understanding of the normal control of GH, well now look at how it can go wrong..
Hypersecretion of GH
Hypothalamus
In a few people, the pituitary continues to secrete GH independently of the normal regulatory mechanisms. The levels of GH increase above normal, leading to excess bone growth and organ enlargement.
GHRH
Somatostatin
Pituitary GH
IGF-1
Liver
Diabetes
Understanding how the system works also gives us an insight into where the control mechanisms can break down Lets look at a growth disorders such as short stature as an example.
Hypothalamus
GHRH
So there is a Problems can occur in the pituitary e.g. defects in complex, or bioactivity GH secretion hierarchical control system and problems Problems can occur in the ability of cellscan occur at any to produce IGF. of the levels
Problems can occur in the target organs e.g. defects in growth response
Somatostatin
Pituitary
GH
Liver
IGF-1
These tests are often called Challenge tests because they are designed to challenge the normal operation of the system..
Challenge Tests
1. Hypothalamic releasing factors, e.g. TRH and GnRH, are useful to identify specific functional cell types in the anterior pituitary (thyrotrophs and gonadotrophs), but this test cannot be used for diagnosis of hypopituitarism or hyperpituitarism.
Note the rapid FSH response when GnRH is given to normal subjects
And the same dose of GnRH results in similar rapid rises in LH
FSH mU/L 8 6 4
10 2
-15
0 20 60 Time (minutes)
90
-15
0 20 60 Time (minutes)
90
Challenge Tests
2. Synthetic drugs can be given to investigate whether the negative feedback control of the anterior pituitary is working properly ( e.g. dexamethasone (suppresses ACTH) and metyrapone (blocks cortisol secretion))
Normal negative feedback control of ACTH by cortisol secreted by the adrenal cortex Dexamethasone suppresses ACTH secretion by the anterior pituitary Metyrapone blocks cortisol secretion from the adrenal cortex
DEX
ACTH
Cortisol Cortisol
ACTH Cortisol
ACTH
Metyrapone
Plasma ACTH = 10 pmol/L Plasma ACTH = 2 pmol/L Plasma ACTH = 37 pmol/L+
Note the increased level of ACTH due to blockage of cortisol secretion and therefore removal of negative feedback control
Challenge Tests
3. The use of a physiological stimulus, e.g. insulin-induced hypoglycaemia, (insulin tolerance test) can be used to help define defects in the system
For example, in normal patients, insulin-induced hypoglycaemia activates hypothalamic neurones to stimulate pituitary secretion of corticotrophin, GH and prolactin.
5
Plasma Glucose 3 (mmol/L) 1
800
Plasma 600 Cortisol (nmol/L) 400
But, in subjects with hypopituitarism, plasma cortisol and and serum GH levels are far below normal levels.
30
60
90
120
30
60
90
120
Time (minutes)
Time (minutes)
Understanding the normal control of the hypothalamic-pituitary axis allows the system to be manipulated to achieve different aims
Lets use the control of reproduction by GnRH, LH, FSH and ovarian hormones as an example..
Control of reproduction
Hypothalamus
The basic operation of the hypothalamic-pituitary-gonadal system is shown opposite. GnRH drives FSH production from the pituitary, and FSH stimulates follicle growth. Oestradiol produced by the follicle provides negative feedback.
+
Pituitary
GnRH
Oestradiol
LH FSH
Ovary
Understanding this system allowed forms of contraception to be developed ..
Control of reproduction
Hypothalamus
The negative feedback control of oestrogens was the original basis of the oral contraceptive pill
Oral oestrogens
GnRH
Pituitary LH FSH
High doses of oestrogens act on the hypothalamic-pituitary axis to suppress LH and FSH secretion and so suppress follicle growth and prevent ovulation
Oestradiol
Ovary
Ovary
Growth of more follicles
GnRH
Pituitary FSH Oestradiol
Ovary
Growth of more follicles
GnRH
Pituitary LH FSH
Clomiphene Oestradiol
Therefore, clomiphene is often used as a fertility treatment for women to increase the number of follicles growing and ovulating
Ovary
Growth of more follicles