3.4 Posterior pituitary hormones Flashcards
posterior pituitary:
- also called what?
- contain what nuclei with ___________ neurons that extend to what?
- which 2 hormones are produced from which nuclei?
- neurohypophysis
- contain hypothalamic nuclei with magnicellular neurons (neurons with large bodies) –> extend their acons to posterior pituitary gland
1. oxytocin (OXT) from PVN nucleus (contains both magnicellular (OXT) and parvicellular/small neurons (CRH, TRH, somatostatin, opioids)
2. vasopressin/anti-diuretic hormone/arginine vasopressin from supraoptic nucleus (SON) –> 805 of neurons produce AVP
posterior pituitary hormone
- what type of hormone?
- structure
- how are they synthesized?
- regulated how?
- stored where? for how long?
- how is pig vasopressin different?
- nonapeptides! proteins with 9 aa
- oxytocin and ADH are structurally similar –> formation of ring via Cys-Cys disulfide bridge
- prohormone (longer hormone) is cleaved as vesicles traverse through the axons
- regulated at transcription and release
- stored in granules (large neurons are so big that you can see granules moving along axon) –> enough for 30-50 days
- PIGS have lysine vasopressin: lysine at 8th position instead of arginine
what are the main roles of vasopressin (2) and oxytocin (3)?
VASOPRESSIN:
- H2O retention by kidneys
- contraction of smooth muscles around blood vessels (arterioles)
OXYTOCIN:
- contraction of smooth muscle cells: myoepithelial cells of the alveoli (around mammary gland) + smooth muscle cells of uterus during labor
- also has a role in luteolysis!
- what (2) indicate the strength/concentration of a solute in a solvent? difference between the 2?
- normal blood value of one of the 2 for homeostasis?
- osmolarity (osmol/L)
- osmolality (osmol/kg)
- normal osmolality: 280-295 mOsm/kg
- what detects osmotic changes in blood? via what organ?
- these things respond to as little as __% change in osmolality
- these things are most sensitive to which electrolyte?
- osmoreceptors located in hypothalamus –> via circumventricular organ OVLT in PVN entities
*OVLT = specific area with more blood supply and that is more permeable than BBB - 1% change!
- sodium!
increase or decrease volume + increase or decrease ionic strength for:
- hypotonic
- hypertonic
*what is the name for homeostatic osmotic pressure?
HYPOTONIC:
- increase volume or decreases ionic strength
HYPERTONIC:
- decrease volume or increase ionic strength
*isotonic
what are the 2 ways to regulate osmolality?
- overall blood pressure and volume regulation involves (3) hormones
- control/conservation of water (through sweat and urine)
- regulation of thirst
- by renin, angiotensin and aldosterone
vasopressin (ADH)
- name is derived from which 2 physiological systems that are regulated?
- what are its 3 ish receptors + target cells + functions?
- basal plasma concentrations?
- half-life?
- vasopressin = constricts blood vessel = vasoconstriction
VS anti-diuretic: promotes water retention/inhibit diuresis in kidneys
1. receptor V1a –> smooth muscles (vasoconstriction) + platelets (platelet aggregation) + hepatocytes (glycogenolysis)
2. receptor V1b –> anterior pituitary –> ACTH release
3. receptor V2 –> collecting tubule in kidney (aquaporin (AQP2) synthesis and translocation) and endothelium (vWF and factor 8 release) - 0.5-2 pg/mL –> really small
- 15 minutes half-life = not long
explain the 2 receptor signaling pathways for vasopressin
- V1a or V1b receptor in vascular and uterine smooth muscle and anterior pituitary:
- GPCR –> Gqa –> phospholipase C –> IP3/Ca2+/DAG pathway –> leads to release of calcium –> calcium in important 2nd messenger for any release! + contraction - V2 receptor in collecting duct:
- GPCR –> Gsa –> adenylyl cyclase –> cAMP, PKA –> expression of APQ2 + insertion in membrane in a specific direction to allow water to be reabsorbed!
anatomy of a nephron:
- which part is juxtaposed to the afferent/efferent arterioles?
the distal convoluted tubule!
how does vasopressin correct low blood volume? 3 steps for the kidney + what else happens?
- in the nephron, blood gets filtered through bowman’s capsule
- cells of distal tubule expresse V2 receptor –> if vasopressin is present –> leads to synthesis and insertion of AQP2 on tubular lumen filtrate
- increases permeability of luminal membrane to H2O –> water moves from tubular lumen filtrate to distal tubular cells + another receptor allows water to cross basal membrane and enter peritubular capillary plasma (aka blood) = increased blood volume –> increased arterial blood pressure
+ vasopressin leads to vasoconstriction = increased arterial blood pressure
water loss from body:
1. through ________ production –> can vasopressin stop it?
2. insensible water loss through (2)
- through urine production –> vasopressin can reduce water loss to a minimum BUT cannot stop it (urine formation will always continue)
- insensible water loss from respiration and perspiration
THIRST:
- what is it?
- triggered by (2) –> strongly triggered by (2)
- mechanisms similar to _________ secretion –> mechanisms well understood? what 2 are important!
- defence mechanism to replace water loss
- triggered by changes in osmolarity or volume –> hypovolemia (low blood volume) or decrease in blood pressure
- similar to vasopressin secretion (but vasopressin doesn’t have any effect on thirst) –> not well understood apart that osmoreceptors and hypothalamus are important
vasopressin and thirst: big schéma:
- what leads to increased thirst? –> what does it do? relieves what?
- what leads to increased vasopressin? –> what does it do? –> relieves what?
- increased osmolarity –> sensed by hypothalamic osmoreceptors –> tell hypothalamic neurons to increase thirst
- increased thirst –> increase water intake –> decrease plasma osmolarity –> relieves the increase in osmolarity (feedback loop)
- decrease ECF volume –> decrease arterial pressure –> sensed by left atrial volume receptors –> tell hypothalamic neurons to increase vasopressin
- vasopressin leads to arteriolar vasoconstriction –> relieves the decrease in arterial blood pressure
- vasopressin also leads to increase water permeability of distal and collecting tubes –> increase water reabsorption –> decrease urine output –> decrease plasma osmolarity + increase plasma volume –> relieves decrease in ECF volume
what happens to thirst signals and vasopressin during pregnancy?
- what physiological thing happens?
- how does body adapt? (2)
- pregnancy –> blood volume can increase by 20-100% (avg 45%)
1. consequently, osmostat (osmotic receptors) is reset/less sensitive + volume and pressure are reset –> so that the expanded volume is sensed as “normal” + vasopressin responds to reset point (treats new volume as normal)
2. placenta also produces an enzyme that degrades vasopressin around wk 20-40 –> decreases vasopressin half-life = less water reabsorption
*can lead to diabetes insipidus of pregnancy (overproduction of urine) if enzyme that degrades vasopressin is over-expressed
what happens to thirst signals and vasopressin in elderly?
- physiological change?
- consequences (4 )
- elderly are thus more susceptible to (2)
- by age 80, total body water declines to as low as 50% of adult
1. decrease filtration rate of kidney –> decrease urine output
2. collecting duct is less responsive to vasopressin = decrease in water reabsorption
3. decreased response to dehydration
4. reduced ability to excrete water load
*elderly are more susceptible to both hypo and hypernatremia (aka hypo or hypervolumia)
what is diabetes insipidus?
- 5 causes
- excretion of a large volume of urine (diabetes) that is hypotonic, dilute and tasteless (insipid)
1. lack of vasopressin (trauma, tumor) –> not water reabsorption = dilute urine
2. lack of response to vasopressin in kidney –> receptor is present but not good signaling
3. receptor defect or aquaporin defect
4. rapid metabolism of vasopressin (ie in pregnancy)
5. pregnancy –> transient diabetes insipidus –> everything goes back to normal after partuition
polydipsia vs polyurea?
- polydipsia = individual drinks too much
- polyurea = individual urinates too much
OXYTOCIN:
- regulation different among species?
- mainly released where? but also (2)
- mostly works by negative or positive feedback?
- regulated by (3)
- physiological regulation of oxytocin secretion is complicated! + differences among species!
- mainly released by posterior pituitary but also by ovaries (CL –> involved in luteolysis) + uterus in some species
- positive feedback!
1. regulated by suckling stimulus
2. regulated by stimulation of cervix
3. regulated by estrogen receptor in uterus/ovary
- function of oxytocin?
- oxytocin becomes responsive at what stage of pregnancy?
- contraction of smooth muscle around uterus (uterine myometrium) during parturition
- relaxed during pregnancy –> progesterone (from placenta/CL) and relaxin (hormone from cervix) inhibit uterine contraction
- uterine myometrium becomes responsive to oxytocin as parturition approaches –> increased # of OXT receptors + formation of gap junctions (synchronus contraction)
- oxytocin works in concert with which hormone?
- oxt knockout mice have almost normal ________ but don’t show any ______ _______. why?
- works in concert with prostaglandin F2a
- almost normal parturition (bc multiple hormones control it! prostaglandin, estradiol…) BUT don’t show any milk ejection (bc oxytocin is the only hormone regulating it!)
what is the pathway/receptor for oxytocin? leads to what?
- GPCR –> Gqa –> phospholipase C –> IP3 + DAG –> calcium release!
- calcium stimulates myosin light chain kinase (MLCK) through calmodulin
- MLCK (kinase = phosphorylation) –> induces smooth muscle contraaction
- what is it called when there is a decrease in 1 or more pituitary hormones?
- describe symptoms of:
1. ACTH deficiency
2. TSH deficiency
- hypopituitarism
1. ACTH –> decrease in adrenal function: malaise, fatigue, anorexia, hypoglycemia
2. TSH –> decrease in thyroid hormones –> malaise, leg cramps, fatigue, dry skin, cold intolerance (bc TSH is regulated by temp)
- describe symptoms of:
1. GH deficiency
2. gonadotropin deficiency
3. PRL deficiency
- GH –> decreased muscle strength and exercise tolerance, diminished libido, increased body fat, growth is inhibited
- gonadotropin –> oligomenorrhea (lower # of menstrual cycles)/amenorrhea, diminished libido, infertility, hot flashes, erectile dysfunction
- PRL –> infertility in both male and female, axoospermia in men (reduced sperm count)
- what is it called when there is over-secretion of hormones of anterior pituitary?
- most commonly due to what?
- these things can arise from 2 ways
- which 3 hormones are the most affected?
- vs which 2 hormones are least common/more rare?
- hyperpituitarism!
- due to benigh tumors of the pituitary = adenomas
- tumors arise de novo OR because of lack of feed-back control (= more stimulation of hormones = overgrowth of tissues
- tumors secreting PRL, GH or ACTH are the most common
- tumors secreting TSH and gonadotropins are rare
- pituitary adenomas: benign or malignant tumors?
- micro vs macro adenomas?
- typically fast/slow growing
- arise from which cells?
- prevalence?
- functional vs non-functional tumors more common for which population groups?
- benign!
- micro (< 10mm) vs macro (> 10mm)
- slow growing = hard to diagnose
- from anterior pituitary cells (bc posterior pituitary are just nerve endings and glial cells)
- 20/100 000
- functional (producing hormones) tumors more common at younger age VS non-functional (don’t produce hormones) more typical in older patients
symptoms of oversecretion of:
1. prolactin (name of disease ish?)
2. GH
- prolactinoma! –> oligo/amenorrhea, galactorrhea (milk production not associated with parturition/nursing)
+ for men and post-menopausal women: infertility, decreased libido, headaches, visual field defects - GH-secreting tumors –> if before end of vertical growth = gigantism VS after vertical growth = acromegaly (prominent supraorbital ridge, large nose and jaw, abnormal glu tolerance test, cardiomegaly…)
+ IGFs elevated consequently!
what is the mass effect?
- consequence?
mass effect = pituitary tumor that puts pressure on bone + on visual tract!
- impingement on optic chiasm –> leads to visual field defects: diplopia (double vision), ptosis (drooping eyelids), altered facial sensation
- how to diagnose pituitary adenomas? (3)
- usually fast diagnosis?
- can tests reveal whether adenoma is hypo or hyperfunctional?
- MRI imaging + blood tests (to see hormone concentrations) + tests for visual field defects!
- usually delayed diagnosis due to non-specific nature of many symptoms –> bc pituitary regulates legit every other organ…
- tests can reveal whether adenoma is hypo or hyperfunctional
how to diagnose deficiency of:
1. GH (3)
2. gonadotropin (3)
3. ACTH (3)
4. TSH (2)
- GH: insulin tolerance tests (GH works opposite of insulin), GHRH/arginine response (inject and check if there’s a GH response), IGF-1 levels
- gonadotropins: sexual history, menstrual history, FSH/LH/estradiol/ prolactin/testosterone levels
- ACTH: AM cortisol, cosyntropin test (ACTH), insulin tolerance test
- TSH: T4 and TSH levels
how to treat pituitary adenomas?
- typically what?
- treat prolactinoma?
- treat acromegaly?
- treat deficiency states
- typically requires surgical resection of adenoma –> access pituitary gland through nose
- prolactinoma (increase in PRL): dopamine agonist therapy –> treat with bromocriptine: binds and activates dopamine receptors –> inhibits PRL secretion
- acromegaly/GH increase –> somatostatin analogs (octreotide)
- deficiency state require replacement of indicated hormone
- what could cause lower testosterone synthesis or action?
- defective protein in any step of testosterone synthesis pathway (ie StAR, CYP17A1, CYP17A1, HSD3B2, HSD3B2, SRD5A) OR problem in androgen receptor (androgen insensitivity syndrome)
consequence/symptoms for lower testosterone synthesis or action
- explanation of how it happens
+ 3 ish consequences
example for testicular feminization (androgen insensitivity syndrome)
- phenotypic female by XY! –> has determining gene = development of testes BUT defective/no synthesis of testosterone –> testes don’t descend/are retained in abdominal cavity + no further development of mal reprod tracts bc requires testosterone!
- testes are present but cryptorchidism (retained in abdominal cavity)
- infertile
- blind ending vagina (bc no uterine tract development)
what are the 3 main signs for PCOS?
what is PCOS?
- which other hormone might be related to PCOS?
polycystic ovary syndrome
1. hyperandrogenism (HA) –> higher than normal testosterone/androgens
2. polycystic organ morphology (ultrasonography –> multiple main follicles!)
3. ovulatory dysfunction (OD): amenorrhea, abnormal menstrual cycles
- insulin! –> visceral adiposity + adipocyte dysfunction –> increase insulin –> insulin resistance –> might lead to hyperandrogenism –> causing abnormal GnRH pulsation + increase LH/FSH ratio –> leading to abnormal ovarian function –> leading to PCOM
