Pituitary Physiology Flashcards
Dopamine action?
PIH Inhibits prolactin release and to a lesser extent GH
Somatostatin
GHIH inhibits release of GH and to a lesser extent prolactin
Hypothalamus effect of GH axis
GHRH is released by hypothalamus and stimulatory for GH GHIH (somatostatin) is inhibitory of GH release –> acts through GPCR to decrease cAMP and activate K+ channels - dopamine inhibits GH release (less)
Anterior pituitary effect of GH axis
GHRH receptor located on somatotrophs (GPCR) –> hormone binding induces release of GH Growth Hormone (somatropin)
Growth Hormone
Somatropin –> bound to GHBP in serum (levels of GHBP indicate tissue levels of GH receptor) GH receptor (tyrosine kinase) –> JAK/STAT pathway –> phosphorylation - promotes growth of all tissues through metabolic effects
GH Axis Target Cells
several isoforms of GHR - liver produces insulin-like growth factor-1 (IGF-1) –> somatomedin - IGF-1 stimulated by GH –> stimulates chondrogenesis at epiphyseal growth plates Growth can be antagonized by cortisol (stress)
GH actions on protein/mineral metabolism
- increases AA uptake and protein synthesis - retention of nitrogen, phosphorus, potassium - increases mineral density in bones after longitudinal growth and epiphyses have closed
GH on carbohydrate/fat metabolism
GH decreased carbohydrate utilization –> hyperglycemia - reduced uptake of glucose, increased liver gluconeogenesis, secondary insulin release GH increases mobilization of fats for energy (lean)
Etiology of Growth Hormone Hyposecretion
KIDS
severe GH deficiency leads to dwarfism (proportional)
- gene mutation in GH axis
- Laron syndrome = autosomal recessive GH receptor variant (insensitive to GH)
- SHOX - short stature homeobox on X
GH Deficiency in Adults
generalized obesity
reduced muscle mass
asthenia
reduced cardiac output
Clinical Assessment of GH deficiency
random samples not useful (pulsatile pattern)
IGF-1 levels –> below 2.5th percentile is consistent with GH deficiency
Insulin-Tolerance Test = administration of insulin to induce hypoglycemia which should stimulate adrenal glands to secrete cortisol and GH - failure suggests GH replacement therapy
Glucagon Test = administration of glucagon -> hyperglycemia -> subsequent hypoglycemia -> stimulate GH = failure means GH replacement therap
Therapetuic use of GH for hyposecretion
promote growth
- goal is to give GH to maintain IGF-1 and IGFBP3 in normal range
Indications for proper dosing
Kids - growth
Adults - lipid profile, fasting glucose, bone density
Side Effects from GH
Scoliosis during rapid growth
Diabetogenic
Hypersecretion of GH
usually pituitary tumor of somatotropes
- increased height and prominent lower jaw, enlarged hands w/ stubby fingers
- results in gigantism and/or acromegaly
Diagnosis of GH Hypersecretion
elevated IGF-1 is first indication
- confirmed by elevated GH level 2 hrs after glucose administration
Treatment of GH hypersecretion
Bromocriptine -> dopamine agonist
Octreotide -> somatostatin analog = longer half-life
GH receptor antagonist
Pegvisomant -> block hepatic GH receptor thereby preventing IGF-1 release -> reduce IGF-1 negative feedback
Prolactin Endocrin Axis
Hypothalamic factors -> prolactin releasing hormone is primary stimulus
Dopamine -> primary inhibitory factor
Anterior Pituitary -> mammotrophs produce and secrete prolactin
PRL chain length
Short chains = silent and soak up PRL -> attenuating signals
Long chains = activating and secreting PRL
PRL physiologic effects
immunity and autoimmunity
- breat development during pregnancy
- milk secretion during lactation -> inhibited by high progesterone
Hypothalamic regulation of PRL secretion
under tonic inhibition by hypothalamus -> dopamine (PIH) by D2 receptors
Prolactin releasing hormone is stimulatory
**If pituitary portal system is blocked/severed, piuitary prolactin secretion increases while all other hormones decrease
**no negative feedback with increasing prolactin levels
Prolactin Hypersecretion
pituitary tumors (disruption of tonic inhibition)
- not associated with pregnancy/lactation
Males = impotence
Females = amenorrhea, galactorrhea, infertility
all due to supression of gonadotropin releasing hormone
Tx = D2 agonists (inhibition)
