Flashcards in The Hypothalamus-Pituitary Complex Deck (59):
What does the HP axis regulate?
The function of the thryoid, adrenal and reproductive glands
Growth, lactation, milk secretion and water metabolism
Where is the pituitary?
In a pocket of bone at the base of the brain below the hypothalamus close to the medial eminence
Connected to hypothalamus and is connected by a stalk containing nerve fibres and blood vessels
What are the key features of the anterior and posterior pituitary?
Anterior - unique blood supply where releasing factors are secreted into from the hypothalamus
Posterior - blood portal system takes hormones away with direct hormonal secretion from the posterior - not synthesised there however
What is the key role of the posterior pituitary?
body fluid homeostasis and reproductive function
Where are hormones synthesised for secretion by the posterior pituitary?
Magnocellular neurons secrete directly into pituitary
Paraventricular nuclei - oxytocin
Supraoptic nuclei - ADH
What are the pre-prohormones of the posterior pituitary?
What are Herring Bodies?
Axonal swellings due to the storage of secretory granules
What are the main functions of ADH?
Maintenance of normal osmolarity of body fluids
Normal blood volume
What are the primary targets of ADH?
Cells lining the distal renal tubule
Principle cells of the collecting ducts in the kidney
How does ADH act on the signalling pathways?
Binds to V2Rs on basal side of renal cells
V2R is linked to Gs-cAMP-PKA pathway
Stimulates insertion of Aquaporin 2 to apical membrane
Enhances trans-epithlial flow of water from lumen to renal interstitium
What happens in the presence of ADH?
Urine flow decreases
Urine Osmolality increases
What is ADH released in response to?
increased EC fluid osmolality
decreased blood volume and pressure
How do osmoreceptive neurons respond to changes in osmolality?
Respond to changes by shrinking or swelling
Innervate magnocellular neurons of PVN and SON
Increased osmolality stimulates ADH releases
How is blood volume regulated?
Cardiovascular volume receptors in the atria
What is the function of oxytocin?
stimulates the contraction of uterine smooth muscle during labour
What is the positive feedback mechanism related to oxytocin?
Stretching of the cervix stimulates oxytocin release which in turn facilitates labour further as a neuroendocrine reflex
After birth, stretching of cervix lessens, breaking the cycle
How is the anterior pituitary connected to the hypothalamus?
hypophyseal portal circulation
What kind of hormones are produced in the anterior pituitary?
What hormones does the anterior pituitary produce?
How are hormones released from the pituitary?
paravicellular neurosecretory cells secrete releasing factors into the capillaries of the pituitary portal system at the median eminance
What are the releasing factors associated with the hormones released?
CRH - ACTH
TRH - TSH
GHRH - GH
Somatostatin - inhibits GH
GnRH - FSH, LH
PRH - Prolactin
Dopamine - inhibits prolactin
What percentage of cells are corticotrophs and what are their target organs?
15-20% - adrenal glands, adipocytes and melanocytes
What percentage of cells are thryotrophs and what are their target organs?
3-5% - thyroid gland
What percentage of cells are gonadotrophs and what are their target organs?
10-15% - Gonads
What percentage of cells are somatotrophs and what are their target organs?
40-50% - All tissues, liver
What percentage of cells are lactotrophs and what are their target organs?
10-15% - breasts, gonads
What is the key feature of the feedback regulation in the HP-axis?
the ability of hypothalamic releasing hormones to provide negative feedback on the system
What is TSH?
a glycoprotein heterodimer composed of an a and b subunit
Where does TSH bind?
thyroid epithelial cells with TSH receptors
How is TRH released?
according to diurnal rhythm and regulated by various stresses i.e. starvation
What does T3 negatively feedback on?
the thyrotropes and TRH-producing neurons
What is the role of thyroid hormone?
regulates the body energy metabolism
What are the main targets for thyroid hormone?
brain, muscle, cardiovascular system and reproductive tissue
How does GH act on tissues?
directly on peripheral tissues and indirectly via IGF-1
What are the main sites for GH degradation?
Kidney and Liver
How is GH secretion regulated?
GHRH stimulates release
Somatostatin inhibits GH and TSH
How might b-adrenergic receptors inhibit GH secretion?
stimulate somatostatin which inhibits GH
What are the pathological conditions involving GH?
dwarfism, gigantism, acromegaly
How is ACTH synthesised?
CRH promotes POMC gene expression which produces ACTH by proteolytic processing
What is the role of ACTH?
to regulate the stress response by regulating the adrenal cortex and the synthesis of adrenocorticosteroids
What is a-MSH?
the first 13 aa in ACTH which stimulate melanocytes and can darken skin when ACTH is over-produced
How is ACTH regulated?
CRH, ADH, stress, hypoglycaemia
ADH via inferior hypophyseal artery from pituitary
How is ACTH secreted?
according to circadian rhythm although can be altered by jetlag
Stress both neurogenic and systemic stimulate ACTH secretion
How does cortisol act to negatively regulate ACTH?
negatively feedback on pituitary reducing POMC expression and hypothalamus reducing pro-CRH gene expression and CRH release
What is Cushing's disease?
a benign tumour of the pituitary gland that produces a large amount of ACTH causing adrenal glands to produce elevated levels of cortisol
What does increased cortisol secretion do?
causes a tendency:
weight gain characteristically in centripetal fat distribution
wasting of extremities, bruising easily and healing poorly
high BP, severe fatigue and muscle weakness
What regulates LH?
What regulates FSH?
GnRH and Inhibin cause distinct patterns of LH and FSH secretion
When does GnRH preferentially increase LH?
at one pulse per hour
When does GnRH preferentially increase FSH?
at 1 pulse per 3 hours
What are the different feedback mechanisms for LH and FSH in men and women?
men - testosterone on pituitary and hypothalamus
women - progesterone on pituitary and hypothalamus
oestrogen on FSH and LH secretion
Inhibin negatively feedsback on FSH in men and women
What is the action of LH in men?
stimulates leydig cells to synthesise testosterone
What is the action of LH in women?
acts on theca cells to produce testosterone which is converted to oestrogen by granulosa cells
What is the function of FSH in women?
stimulates maturation of ovarian follicles
what is the function of FSH in men?
supports the function of the sertoli cells which support aspects of sperm cell maturation
How are FSH and LH regulated?
dopamine, endorphins and prolactin all inhibit GnRH release
What can overproduction of prolactin cause and how might this be treated?
treat with bromocryptine or surgical removal of tumour
What stimulates ovulation?
high plasma estadiol which stimulates GnRH and LH surge