Posterior Pituitary and HPL Axis Flashcards
What is the AVP pro hormone comprised of?
AVP + neurophysin II
What is the oxytocin pro hormone comprised of?
Oxytocin + neurophysin I
What are the two types of cells found in the paraventricular nucleus (PVN)?
Parvocellular
Magnocellular
What are the only PVN cells to project to the posterior pituitary?
Magnocellular Neurons
Where do parvocellular PVN neurons project to?
Median Eminence
When does the cleavage of neurophysin from released hormones occur?
Neurophysin is cleaved from the prohormone in the secretory granules during axonal transport.
What are the main targets of AVP?
Kidney and vasculature
What is the most potent stimulus for the release of AVP?
Osmolarity
What is the effect of AVP on the vasculature?
Causes vasoconstriction
What is the effect of AVP on the kidney?
Leads to aquaporin insertion in the distal tubule that leads to increased H2O reabsorption
What is the effect of AVP on the sympathetic nervous system?
Increases sympathetic tone
What receptor pathways does AVP go through to cause vasoconstriction?
Phospholipase C -> Ca2+ -> Calmodulin -> MLC Kinase
What is the major symptom of diabetes insipidus?
Excessive urination
What is the most common cause of diabetes insipidus?
Decreased AVP release which is due to a hypothalamic or pituitary defect “central” due to trauma, cancer, or infectious disease.
Besides a hypothalamic or pituitary defect, what may be the other cause of diabetes insipidus?
Decreased renal responsiveness to AVP that can be either genetic OR acquired.
Besides a hypothalamic or pituitary defect, what may be the other cause of diabetes insipidus?
Decreased renal responsiveness to AVP that can be either genetic OR acquired.
Genetic - X linked mutation in the AVP receptor
Acquired - Li treatment or hypokalemia
AVP levels are NORMAL in BOTH genetic and acquired diabetes insipidus.
What is pitocin?
It is artificial oxytocin used to stimulate labor
What does the oxytocin receptor activate?
It is a GPCR that activates PLC and IP3 -> Ca2+ signalling
What is the function of oxytocin?
Induces smooth muscle contration in breast and uterus for milk ejection and birth
How are the structure of AVP and OXY similar?
They are both 9 AAs and only differ by a single AA
What is the HPL axis comprised of?
Hypothalamic Arcuate Nucleus - GHRH
Pituitary Somatotroph - GH
Liver - IGF-I
What is the function of GHRH?
It is made in the arcuate nucleus and functions to stimulate the release of GH from the anterior pituitary.
What are the two forms of somatostatin?
There is SS14 and SS28
SS14 is found in the hypothalamus and SS28 is found in the D cells of the stomach
What is the function of somatostatin in the brain?
Inhibits GHRH at the hypothalamus
Inhibits GH and TSH in pituitary
Describe the release of somatostatin and its timing.
It has a pulsatile release that occurs normally at night
What stimulates IGF-I production in the liver?
GH
What is the function of IGF-I?
Insulin-like growth factor mediates the downstream effects of GH and also as negative feedback to INHIBIT GH release.
What is the effect of IGF-I on various tissues like muscle/adipose/liver?
IGF-I acts like insulin in muscle but does not in adipose or liver because they do not have the receptors.
At what age range does IGF-I reach its peak?
During puberty
What are some of the direct effects of GH?
Decreases adiposity
Increases gluconeogenesis/protein synthesis
Increases lean body mass
What are the effect of IGF-I (indirect effects of GH)?
Increases organ size and function
Increases linear growth
What is the cause and effect of gigantism?
GH excess often due to a somatotroph tumor.
This occurs before the closing of the epiphyseal plates and results in long bones.
What is the cause and effect of acromegaly?
Similar to gigantism, but occurs around middle age.
Gradual enlargement of hands and feet – leads to arthritis
Changes in facial features – protuding lower jaw, enlarged lips, tongue, and nose.
Possible increased organ size
Most often caused by pituitary adenoma
What is Laron Syndrome?
It is a form of dwarfism caused by a genetic defect in GH receptor so there is no production of IGF-I.
Treatment with IGF-I can prevent dwarfism.
Plasma GH levels are normal to high (lack of feedback).
What is African Pygmy syndrome?
It is a form of dwarfism caused by a partial defect in GH receptor that results in some IGF-I response.
Plasma levels of GH normal as the IGF-I is produced and enacts negative feedback, but there is no pubertal increase in IGF-I so growth stops here and it is hard to diagnose as children are normal until this point.
What is the function of prolactin and its role in endocrine axes?
Lactotropes are not part of an endocrine axis – short loop feedback on hypothalamic dopamine; no unique stimulating factor from hypothalamus.
What is an inhibitor of prolactin?
Prolactin is tonically inhibited by dopamine – early antihypertensive drugs inhibit dopamine —- increased prolactin (galactorrhea)
How is prolactin transported in the blood?
Prolactin is not bound to serum proteins and is released in response to the suckling stimulus.
What is prolactin and inhibitor of?
GnRH. It is to prevent ovulation and subsequent pregnancies.
Why can excess GH cause galactorrhea and inhibit reproduction?
GH and prolactin have similar structures that can be recognized by their receptors
What is prolactin excess caused by and its effect?
Prolactinomas – 30-40% of all pituitary adenomas.
Hyperprolactinemia
Galactorrhea – milk production or discharge from breast
Reproductive dysfunction - prolactin inhibits GnRH release
What is Sheehan’s Syndrome?
Occurs as a result of excessive blood loss/shock during childbirth.
Partial pituitary destruction occurs that usually affects other pituitary cell types and leads to loss of axillary and pubic hair and prevents breast feeding due to no prolactin production.
