172. Hypothalamus-Pituitary Basic Flashcards
Describe differences in signaling from hypothalamus to anterior pituitary and from hypothalamus to posterior pituitary
Anterior Pit: stimuli integrated w/in nervous system, hypothalamic neurons secrete Releasing Hormones, hypothalamic-hypophysial portal system transports RHs, RHs stim pit hormone secretion
Post Pit: stimuli integrated w/in nervous system, hypothalamo-hypophseal TRACT stim post pit for hormone secretion
List 8 stimulating and inhibiting releasing hormones and their effect on the anterior pituitary hormones.
Which ant pit hormones are highest at what points throughout the day? Pulsatile v. Continuous?
- AVP (minor) stim to ACTH
- CRH (major) stim to ACTH
- TRH stim to TSH, PRL
- GnRH stim to LH/FSH
- GHRH stim to GH
- VIP stim PRL
- SS inhibits GH, TSH
- DA inhibits PRL
ACTH, Cortisol, TSH, PRL = highest at night
Testosterone = highest in AM
GH = spikes at night
Pulsatile secretions cause pulsatile pit hormone secretions
Continuous secretions cause LOWER pit hormone levels (used to tx high levels of hormone)
Describe the embryonic development of the ant pit and post pituitary. What transcription factors are involved in specific hormone-producing neuron development?
Ant pit: hypophyseal pouch pinches off pharynx (surface ectoderm)
Post pit: neurohypophyseal bud from neural ectoderm
Tbx19 = POMC cells (ACTH, alpha-MSH cells)
Prop1 + Pit1 = TSH, GH, PRL Cells
Prop1 + Gata2/SF1 = LH/FSH
Prolactin
- what factors stim/inhibit hypothalamic secretion? Pit secretion?
- what is target tissue?
- major hypothalamic effect is inhibitory or excitatory?
- when do PRL levels rise? What is PRL effect?
Hypothalamus Stim: Stress (+), Breast Suckling (spinal afferents) (+) Secretes: TRH (+), VIP (+), DA (-) MAJOR EFFECT IS INHIBITORY (cut hypothalamic stalk = RISE in PRL)
Pituitary
Stim: TRH (+), VIP (+), DA (-)
Secretes: PRL to Breast
PRL levels rise in pregnancy to prepare breasts for milk production.
Suckling + PRL cause galactopoiesis (milk production) and galactokinesis (milk secretion)
GH
- what factors stim/inhibit hypothalamic/pit secretions? Where does feedback occur?
- how does the GH receptor work?
- what does the target organ produce? What is that function?
- when do levels rise?
Hypothalamus
Stim: Stress (+/-), GH (-), IGF1 (-)
Secrete: GHRH (+), SS (-)
Pituitary
Stim: GHRH (+), SS (-), IGF1 (-)
Secrete: GH (+) [fb on hypothalamus]
Liver/Bones
Stim: GH (+)
Secrete: IGF1 [fb on hypothalamus, pit]
GH-R: binding = dimerization of receptor subunits, cross-phosphorylation
IGF1: similar to ins (most variability in C-chain), binds IGFBPs in blood (high affinity and specificity, prolong half life, regulate IGF access to receptor in ECF)
Rise in GH + IGF1 during puberty (increase amplitudes of pulsatile secretions) - levels diminish in adulthood
GH/IGF1
- describe effect at site of action in bone
What effect do other hormones have in growth?
What are the sites of GH action, and what is the effect?
Epiphyseal growth plate: GH/IGF1 cause bony growth here; usually seals off due to estrogen (T converts to E = bone plate closure) [deficient E-R: growth plates do not fuse = continued growth!]
T3/T4: hypothyroid: less GH, growth stunting
Ins: deficiency blocks growth, hyperins spurs excess growth
Androgen: role in puberty growth spurt, stim protein synthesis, effects depend on GH presence and aromatization to E
Cortisone (rat study) inhibits GH and slows growth
GH Action
- Bone: increase oclast differentiation/activity, increase oblast activity, increase bone mass by endochondral bone formation
- Muscle: increase AA transport, increase N retention, increase lean tissue and EE
- Adipose: acute ins-like effects, then increase lipolysis, decrease lipogenesis, inhibit lipoprotein lipase, increase HSL (lipolysis), decrease glucose transport
Which hormones are glycoproteins? Why are they similar? Which two are most similar?
TSH, FSH, LH, HCG (placenta) all share common alpha subunit
beta subunit confers specificity (LH and HCG beta subunits look most similar)
TSH
- describe factors stimulating/inhibiting its axis
Hypothalamus
Stim: Stress (-), T4/T3 (-)
Secrete: TRH (+), SS (-)
Pituitary
Stim: T4/T3 (-), TRH (+), SS (-)
Secrete: TSH
Thyroid
Stim: TSH (+)
Secrete: T4/T3 (peripheral conversion T4 -> T3)
LH/FSH
- describe factors stimulating/inhibiting its axis (M vs F)
- what occurs during menses?
FEMALE
Hypothalamus
Stim: Stress (-), E (+/-)
Secrete: GnRH (+)
Pituitary (high Activin, low Follistatin)
Stim: GnRH (+), E/Progesterone (+/-), Inhibin (-)
Secrete: FSH/LH (+)
Ovary
Stim: FSH/LH (+)
Secrete: E (+/-), Progesterone (+/-), Inhibin (-), folliculogenesis/inhibin (activin/follistatin)
Menses: low FSH/LH, low E/P = FSH stim, follicle develops, high E, low FSH/LH (-fb) = higher E causes +fb, high FSH/LH = +fb of High FSH/LH and high E/P (follicle maturation/ovulation) = high P causes (-fb), lowers FSH/LH, decreases E/P, menses
MALE
Hypothalamus
Stim: Stress (-), T (-)
Secrete: GnRH (+)
Pituitary
Stim: GnRH (+), T (-), Inhibin (-)
Secrete: LH/FSH (+)
Testes
Stim: LH/FSH (+)
Secrete: T (-) [peripheral conversion to DHT - active form], Inhibin (-) [spermatogenesis, activin, follistatin]
ACTH
- describe factors stimulating/inhibiting its axis
- what is ACTH precursor? What are other fragments?
Hypothalamus
Stim: Stress (+++), Cortisol (-)
Secrete: CRH (major +), AVP (minor +)
Pituitary
Stim: CRH (+), AVP (+), Cortisol (-)
Secrete: ACTH (+)
Adrenal Gland
Stim: ACTH (+)
Secrete: Androgens, Cortisol (-fb), Aldosterone (under RAAS control)
POMC: precursor of ACTH, needs to be proteolytically cleaved to isolate ACTH, other byproducts are beta-MSH, beta-endorphin, alpha-MSH
AVP
- describe factors stimulating/inhibiting its release
- action of AVP (physiologic - low conc. vs pathologic - high conc)
Stimulus: low BV or high blood OsM
Physiologic (Low Conc AVP): decrease urinary water excretion (antidiuresis) via more water reabsorption in collecting tubules, more AQP trafficking, permitting passive water diffusion to hypertonic medulla [V2 receptors]
Pathologic (High Conc AVP): release of Factor VII and vWF (activate platelets), contract smooth muscle (intestine/skin) = raise BP [V1 Receptors]
Oxytocin
- describe factors stimulating/inhibiting its release
- action of oxytocin on two locations
Stim: suckling of mammary glands OR cervical stretch receptors; cause POSITIVE FEEDBACK through CNS relays to amplify response
Action:
Mammary Gland - suckling = sensory receptors in nipple = nerve fibers to spine-brain-PVN = fire oxytocin neurons to stim oxytocin release = myoepithelial cell contraction & milk ejection
Uterus - oxytocin from fetus/placenta and mother’s post pit = uterus contraction = more oxytocin = more contraction (childbirth)
