Pituitary Physiology

Question 1

Dopamine action?

Answer 1

PIH Inhibits prolactin release and to a lesser extent GH

Question 2

Somatostatin

Answer 2

GHIH inhibits release of GH and to a lesser extent prolactin

Question 3

Hypothalamus effect of GH axis

Answer 3

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)

Question 4

Anterior pituitary effect of GH axis

Answer 4

GHRH receptor located on somatotrophs (GPCR) –> hormone binding induces release of GH Growth Hormone (somatropin)

Question 5

Growth Hormone

Answer 5

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

Question 6

GH Axis Target Cells

Answer 6

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)

Question 7

GH actions on protein/mineral metabolism

Answer 7

• increases AA uptake and protein synthesis - retention of nitrogen, phosphorus, potassium - increases mineral density in bones after longitudinal growth and epiphyses have closed

Question 8

GH on carbohydrate/fat metabolism

Answer 8

GH decreased carbohydrate utilization –> hyperglycemia - reduced uptake of glucose, increased liver gluconeogenesis, secondary insulin release GH increases mobilization of fats for energy (lean)

Question 9

Growth Hormone Endocrine Axis Control

Answer 9

Question 10

Etiology of Growth Hormone Hyposecretion

Answer 10

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

Question 11

GH Deficiency in Adults

Answer 11

generalized obesity

reduced muscle mass

asthenia

reduced cardiac output

Question 12

Clinical Assessment of GH deficiency

Answer 12

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

Question 13

Therapetuic use of GH for hyposecretion

Answer 13

promote growth

• goal is to give GH to maintain IGF-1 and IGFBP3 in normal range

Question 14

Indications for proper dosing

Answer 14

Kids - growth

Adults - lipid profile, fasting glucose, bone density

Question 15

Side Effects from GH

Answer 15

Scoliosis during rapid growth

Diabetogenic

Question 16

Hypersecretion of GH

Answer 16

usually pituitary tumor of somatotropes

• increased height and prominent lower jaw, enlarged hands w/ stubby fingers
• results in gigantism and/or acromegaly

Question 17

Diagnosis of GH Hypersecretion

Answer 17

elevated IGF-1 is first indication

• confirmed by elevated GH level 2 hrs after glucose administration

Question 18

Treatment of GH hypersecretion

Answer 18

Bromocriptine -> dopamine agonist

Octreotide -> somatostatin analog = longer half-life

Question 19

GH receptor antagonist

Answer 19

Pegvisomant -> block hepatic GH receptor thereby preventing IGF-1 release -> reduce IGF-1 negative feedback

Question 20

Prolactin Endocrin Axis

Answer 20

Hypothalamic factors -> prolactin releasing hormone is primary stimulus

Dopamine -> primary inhibitory factor

Anterior Pituitary -> mammotrophs produce and secrete prolactin

Question 21

PRL chain length

Answer 21

Short chains = silent and soak up PRL -> attenuating signals

Long chains = activating and secreting PRL

Question 22

PRL physiologic effects

Answer 22

immunity and autoimmunity

• breat development during pregnancy
• milk secretion during lactation -> inhibited by high progesterone

Question 23

Hypothalamic regulation of PRL secretion

Answer 23

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

Question 24

Prolactin Hypersecretion

Answer 24

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)