2- The hypothalamo-adenohypophyseal axis: anterior pituitary Flashcards
Where is the pituitary positioned
The pituitary is attached to the base of the brain
• It lies within a bone lined cavity - Sella Turcica
• Sella Turcica is important from a clinical point of view because a tumour will be constrained
by the walls of the bony cavity
• Pituitary tumours may protrude out towards
the brain or it may go through the
bone (if it is really malignant)
• The hypothalamus lies just above the
pituitary gland
How does the pituitary form
First few weeks after conception:
Glandular Tissue - Buccal Cavity (pharyngeal region of the mouth) has an extension that starts growing upwards Nervous Tissue - there is a downwards movement of tissue from the developing hypothalamus
These two tissues then fuse and
normally lose contact with the rest of the buccal cavity.
So one part of the pituitary is derived from glandular tissue (adenohypophysis) and the other part is derived from neural tissue (neurohypophysis)
How are the pituitary and hypothalamus linked
In the hypothalamus, lots of bundles
of neurones can be grouped functionally into HYPOTHALAMIC NUCLEI
• Median Eminence = an area that lies between the top of the pituitary stalk and the hypothalamus
• The neurohypophysis is mainly made up of nerve axons
• The cell bodies of these nerve axons lie in the hypothalamus
• Some of the axons coming from the hypothalamic nuclei terminate in the median eminence
How do pituitary hormones get into circulation
The median eminence is essentially a MASS OF CAPILLARIES receiving blood form the superior hypophysial artery
• Lots of neurones coming from the hypothalamic nuclei terminate on the walls of the PRIMARY CAPILLARY PLEXUS
• The primary capillary plexus feeds blood down into portal vessels which run down through the pituitary stalk to terminate within the adenohypophysis
• This is the Hypothalamo-hypophysial portal system
• From here the blood is gathered into the Cavernous sinus and out through the
Jugular veins
• Primary Capillary Plexus - in the median eminence
• Secondary Capillary Plexus - in the anterior pituitary
• The median eminence lies outside the blood-brain barrier meaning that the
capillary walls have lots of holes so they are Fenestrated Capillaries
Describe hypothalamic stimulation of anterior pituitary
Hypothalamic Nuclei sand signal down Neurones to median eminence
Neurones secrete neurosecretions which ARE NOT neurotransmitters, they are HORMONES (inhibiting or stimulating)
Hormones travel in the hypothalamo-adenohypophysial portal system to the anterior pituitary
Adenohypophysial cells are stimulated to release hormones into the circulation
What are the 5 types of cell in the anterior pituitary
Somatotroph (growth hormone) Lactotrophs (prolactin) Thyrotrophs (tsh) Gonadotrophs ( Corticotrophs
How are Adenohypophysial Hormones synthesised
• Synthesised as PROHORMONES
• Enzymatic cleavage of the prohormone yields the bioactive hormone
• Adenohypophysial hormones are stored in secretory granules and released by
exocytosis
• Adenohypophysial cells can also produce other molecules which have paracrine
or autocrine effects
Give examples of PROTEINS, GLYCOPROTEINS or POLYPEPTIDES Adenohypophysial hormones
are PROTEINS, GLYCOPROTEINS or POLYPEPTIDES
• Proteins:
Somatotrophin - 191aa
Prolactin - 199aa
• Glycoproteins: consisting of ALPHA and BETA subunits
Alpha subunit is common to all, Beta subunit is different and hence determines the characteristics of the molecule
Thyrotrophin (Beta subunit - 110aa)
LH and FSH (Beta subunit - 115aa)
• Polypeptide:
Corticotrophin (ACTH) - 39aa
Describe Hypothalamic Hormones and the Adenohypophysial Hormones that they control
•Growth Hormone Releasing Hormone (GHRH, somatotrophin releasing hormone)
•Somatostatin (SS)
Control Growth hormone (somatotrophin)
•Dopamine (DA)
•Thyrotrophin releasing hormone (TRH)
Control prolactin and thyrotrophin
•Gonadotrophin releaseing hormone
•Gonadotrophin releasing
hormone (GnRH)
Control LH, FSH
Corticotrophin releasing hormone
•Vasopressin (VP)
Control ACTH (corticotrophin)
Which hypothalamic hormones are dominant
Somatrotophin Releasing Hormone (SRH or GHRH) - dominant over somatostatin
Dopamine - dominant over thyrotrophin releasing hormone Gonadotrophin Releasing Hormone - dominant over gonadotrophin inhibitory hormone
Describe the action of somatotrophin
Somatotrophin works on many tissues in the body and stimulates various metabolic actions - it is involved in growth
• The liver has endocrine functions and is the main target tissue of somatotrophin
• Somatotrophin binds to receptors on the hepatocytes and stimulates the production of hormone from those cells
• The molecules produced used to be called Somatomedins but are now called Insulin-like Growth Factor (IGF) I and II
• IGF I is particularly important for growth
• Somatotrophin works in two ways:
Direct Effect - binding to somatotrophin receptors in general cells of the body
Hepatocytes - stimulating hepatocytes to produce IGF I
Both these pathways mean that somatotrophin controls large aspects of metabolism
Describe the metabolic effect of somatotrophin
Stimulation of amino acids transport into the cell
• Stimulation of protein synthesis
• Increased cartilaginous growth
• Stimulation of lipid metabolism leading to increased fatty acid production
Decreased glucose utilisation resulting in increased blood glucose concentration
How is somatotrophin controlled
Growth Hormone Releasing Hormone is the main one from the hypothalamus - somatostatin has the opposite effect
• Certain glucogenic amino acids can stimulate growth hormone release
Makes sense because after a meal you will have lots of amino acids coming in so by stimulating growth hormone release, you increase amino acid movement into the cells and increase protein synthesis at the nuclear level
• HYPOGLYCAEMIA is a potent stimulus for growth hormone release
Makes sense because the ultimate effect of growth hormone is to increase blood glucose levels
• Other things that stimulate growth hormone release:
Exercise Stress Oestrogen Sleep
• NOTE: Hypothalamic hormones are released in PULSES
• Ghrelin stimulates growth hormone release - comes from the stomach
• Inhibitors of somatotrophin:
Direct - IGF I back to the pituitary
Indirect - IGF I back to the hypothalamus
Somatotrophin also has its own negative feedback effects - back to the hypothalamus - auto-negative feedback loop
Describe the effects of prolactin
MAIN EFFECT = BREAST LACTOGENESIS
• Has an effect on LH receptors on target tissues - when prolactin levels are high
it INHIBITS LH RELEASE
Makes sense because prolactin is released in high amounts when the baby is suckling and during this period the mother would not want to have periods and become pregnant again so prolactin has a natural contraceptive effect
• When prolactin levels are high, sexual behaviour is reduced
• Prolactin also has effects on the immune system
Describe the control of prolactin
Control is brought about by the baby suckling on the breast
• There are tactile receptors on the nipple which are associated with an afferent
nerve pathway - this goes back to the hypothalamus
• Two hypothalamic hormones controlling prolactin release:
Dopamine
Thyrotrophin Releasing Hormone
• When the afferent pathway is stimulated, dopaminergic neurones are inhibited and there is direct stimulation of thyrotrophin releasing hormone - this leads to release of prolactin
• Prolactin starts the synthesis of milk for the next suckling period
• Oestrogens and Iodothyronines also have an effect
