Anterior and Posterior pituitary; Growth Hormone Flashcards
What’s the difference in how neurons signal between the anterior and posterior pituitary?
For posterior pituitary, neurons project directly into the gland and the hormones travel to the bloodstream via the capillary bed
For the anterior pituitary, the neurons don’t project into the ant pit; hormone factors are released into the portal plexus (in the median eminence) then they drift into the ant pit
Name the anterior pituitary hormones, the type of hormone each is, and the cell types that release them
LH and FSH: gonandotrophs; glycoprotein
TSH: thyrotrophs; glycoprotein
GH: somatotrophs (somatomammotrophic)
PRL: lacto/mammotrophs (somatomammotrophic)
ACTH: corticotrophs (POMC derivative)
What are the releasing hormones for the following:
TSH
LH/FSH
GH
ACTH
What are the 2 functions of the releasing hormones? By which mechanism are they activated? T/F: GH and PRL are the exception to this mechanism.
Thyrotropin releasing hormone (TRH) - TSH
Gonadotropin releasing hormone (GnRH) - LH, FSH
Corticotropin releasing hormone (CRH) - ACTH
Growth hormone releasing hormone (GHRH) - GH
Activated via GPCR signaling
True. PRL and GH have a separate pathway
What are the roles of somatostatin and doPamine? (i.e. which hormones do they act on and how)
Somatostatin inhibits GH
Dopamine inhibits Prolactin
Describe the loop below. Give three examples of hormones and target organs involved at each level.
Describe the difference between long, short and ultra short feedback in the hypothalamic-pituitary loop
Long feedback – endocrine hormone feeds back on pituitary and hypothalamus
Short feedback – pituitary hormone feeds back on hypothalamus
Ultra-short feedback – hypothalamic releasing factors feed back on the hypothalamus itself
What are the three hypothalamic axes discussed?
HPG (gonadal) axis
HPA (adrenal) axis
HPT (thyroid) axis
Outline the HPG axis. Which hormones are involved at each level?
What are the functions of LH and FSH in men and women? Between FSH and LH, which one would you test and why?
LH - ovulation, testosterone production
FSH - follicle growth, spermatogenesis
(see diagram below)
Test FSH b/c release is more stable. LH has more pulsatility
What are the effects of pulsatile vs continuous GnRH release? (refer to diagram below)
What’s an example disorder that can be treated by continuous GnRH release?
Continuous release of GnRH – eventually, GnRH receptors are downregulated
Pulsatile release: axis functions like its supposed to
Prolonged GnRH can be used to treat precocious puberty because gonadal axis is suppressed
Describe the HPA axis (plus hormones involved and all that)
What is the effect of CRH on ACTH release and POMC?
What other hormone is formed from ACTH breakdown whose product clues us into a low cortisol/high ACTH problem,like primary adrenal insufficiency?
ACTH and other POMC derived peptides secreted; POMC transcription increased
Melanocyte stimulating hormone (MSH) (hyperpigmentation present in primary adrenal insufficiency)
Subclinical hypo vs hyperthyroidism
Subclinical hypothyroidism (TSH levels slightly high but thyroid levels normal)
subclinical hyperthyroidism (TSH levels slightly low but thyroid levels normal)
Describe the HPT axis.
How are hypothyroidism and prolactin related? (think TSH/T4 levels and downstream effects)
Outline the pathway of GH release.
Which factors stimulate GH release? What inhibits it?
What are the functions of GH? What’s the effect of GH excess?
Stimulated by Ghrelin, free fatty acids
Inhibited by STS
Regulated by IGF1
GH excess = insulin resistance, acromegaly
Relationship between GH and PRL.
What kinds of receptors do they act on? (hint: not GPCRs like the other ones)
Structurally similar, both can be released sometimes (esp by a tumor); GH can activate PRL receptors at high conc but not vice versa
Act on Cytokine receptors
What stimulates PRL release? What inhibits it? Which effect is mostly present?
What’s the main PRL function?
Describe the stalk effect and what happens to dopamine release
Stimulated by estrogen, TRH
Inhibited by dopamine (main effect)
Function = lactation
Stalk effect = inhibition of pituitary stalk, which blocks dopamine effect (other hormones also decreased) >> increased PRL
Name the posterior pituitary hormones
What are the functions of each?
Oxytocin
Vasopressin
Oxytocin: uterine muscle contraction for childbirth + lactation
Vasopressin: free water retention (via AQPs insertion and V2 receptor binding) + vasoconstriction (via V1 receptor activity on smooth ms vasculature)
secondary function of vasopressin - stimulates ACTH release
Describe the graph below. What is the relationship between osmolality and ADH secretion?
What are neurophysins and how are they involved in AVP synthesis?
What happens when you have a defect in neurophysins?
Neurophysins: part of precursor molecule from which AVP is synthesized.
Act as carriers for AVP transport down the axon
Defect: familial neurogenic diabetes insipidus
Describe the direct and indirect effects of GH.
What are the effects of GH on growth (hint: IGF stimulates 2 things) and metabolism (hint: prots, fats and diabetes)
Growth: IGF1 stimulates bone and muscle growth
Metabolism: + protein synthesis, + triglyceride breakdown and oxidation, opposes effects of insulin
Describe how GH release is regulated.
What factors are released from the liver and adipose tissue? what’s they’re effect on GH release?
Which factor from the stomach stimulates GH release?
3 other things that promote GH release (hint: low glucose leaves you stressed; one more thing also)
Adipose tissue - free fatty acids
Liver - IGF1
Both - inhibit GH release at pituitary and hypothalamus level
Ghrelin
Stress, Amino acids, Hypoglycemia
Describe what happens when GH binds to its receptor.
Which drug is GH competitive inhibitor? How does it work?
Growth hormone binding to a site on each dimer – induces conformational change >> stimulates JAK/STAT signaling
Pegvisomant has mutations in the first and 2nd binding sites; binds to the receptors but doesn’t induce conformational change >> no JAK/STAT signaling
What’s the relationship between IGF and Insulin? (i.e. what’s similar about the receptors?)
IGF1/2 and Insulin can all bind to insulin and IGF receptors
Describe what’s shown in this graph
Arginine stimulates GH secretion by inhibiting STS secretion
This experiment: arginine + synthetic GHRH
Growth hormone response here is robust; not a pituitary problem but patient can still be growth hormone deficient
Describe what’s shown in this graph
Induced hypoglycemia (to test hypothalamic function)
In response to severe hypoglycemia; no GH release, therefore problem was hypothalamic (and pt was Gh deficient)
Describe the glucagon test for GH function
Inject synthetic glucagon into pt
Normal pts: GH levels should go up when glucagon injected
When glucose levels go up, insulin is secreted, which then lowers blood glucose and increases GH response
Explain the data below. Why would you do an oral glucose test for acromegaly?
Adding a bunch of glucose should suppress GH (because normally GH promotes blood glucose levels)
