Anterior pituitary hormones

Question 1

Prolactin, LH, FSH and their effects

Answer 1

• Prolactin: promotes milk secretion and maternal behavior
• Prolactin release is NEGATIVELY regulated by DA (only hormone that is regulated via inhibition rather than stimulation)
• Prolactin inhibits GnRH release and thus reduces levels of LH and FSH when prolactin is very high
• LH: in females it stimulates the ovulation, in males it stimulates testosterone secretion
• FSH: stimulates ovarian follicle growth, in males it stimulates spermatogenesis
• Both LH and FSH are controlled by GnRH release from hypothalamus

Question 2

Control of prolactin release

Answer 2

• Primarily controlled by DA: increased DA release from the hypothalamus leads to suppressed prolactin release
• Suckling of the breast stimulates prolactin release
• High levels of estrogen inhibit prolactin release whereas moderate estrogen levels stimulate prolactin release
• Prolactin inhibits GnRH release from hypothalamus and thus reduces LH, FHS, and downstream hormone levels (estrogen, testosterone)
• This helps to delay the next pregnancy by decreasing libido while breastfeeding

Question 3

Control of FSH and LH

Answer 3

• Both lead to the release of estrogen, LH leads to the release of testosterone (in the ovaries or testes)
• Testosterone and estrogen feedback on the pituitary to inhibit FSH/LH release
• Estrogen also will decrease prolactin release at high levels, and stimulate prolactin release at moderate levels

Question 4

Hyper and hypoprolactinemia

Answer 4

• Hypoprolactinemia can result from pituitary damage and produce a failure to lactate (no Rx)
• Hyperprolactinemia is usually from prolactinoma (most common pituitary tumor)
• Rx is DA agonist drugs: bromocriptine and cabergoline

Question 5

Posterior pituitary hormones

Answer 5

• ADH: promotes renal water (and Na) retention
• Central DI: failure of pituitary to release ADH
• Nephrogenic DI: failure of kidneys to respond to ADH
• Oxytocin: acts on breast to eject milk and causes uteral contractions

Question 6

Growth Hormone

Answer 6

• AKA somatotropin, GH is not conserved btwn species thus we must give human GH (hGH) as Rx
• Synthesized in anterior pituitary and accounts for 10% of its weight
• GH circulates bound to a carrier
• Pulsatile GH Rx is more effective than continuous GH (is released in a pulsatile manner in vivo)

Question 7

Effects of GH

Answer 7

• GH spares glucose utilization, increases availability of FAs, promotes AA uptake and protein synthesis
• Free FA increase will decrease vlc utilization and make tissues resistant to insulin
• GH is diabetogenic (spares glc, favors burning of fat) despite causing the release of IGF1, which can increase glc uptake and utilization
• GH promotes growth in size of limbs and internal organs
• GH is one of the primary hormones that regulates protein synthesis (increases it)

Question 8

IGF1

Answer 8

• IGF1 is released in the liver in response to GH and has a number of effects
• One of primary purposes of IGF1 is to regulate glc uptake and utilization in the fasted state (when insulin is suppressed)
• Insulin also causes the release of IGF1, so it does play a role in the well-fed state
• IGF1 and IGF2 (less important) are similar in structure to insulin, but the C peptide remains on IGFs
• IGF1 is the primary IGF that regulates growth

Question 9

Roles of GH and IGF

Answer 9

• Increase of GH causes the liver to increase GNG (diabetogenic), protein synthesis, and IGF release
• In adipose tissue, GH causes decreased glc uptake and increased lipolysis (both are diabetogenic)
• In muscle GH causes decreased glc uptake (diabetogenic), increased AA uptake, and increased protein synthesis
• In bone IGF1 causes increased linear growth and increased cell size/number
• In other organs IGF causes increase cell size/number

Question 10

Regulation of GH release 1

Answer 10

• GH primarily controlled by the hypothalamus via GHRH (positive regulation) and somatostatin (negative regulation)
• Increase in GHRH and/or a decrease in somatostatin causes GH release, leading to a rise in IGF
• IGF feeds back to pituitary (shuts off GH release) and hypothalamus (increases somatostatin thus decreases GH release)
• GH feeds back to hypothalamus to increase somatostatin release and reduce GH release

Question 11

Regulation of GH release 2

Answer 11

• GHRH negatively feeds back on itself
• Fasting and high protein meals increases GHRH release
• High glc increases somatostatin release and decreases GH
• Hypoglycemia causes GH release (insulin induced or fasting)
• Insulin-induced hypoglycemia can be used to test for normal GH response
• Decreased FFA levels will increase GH release
• Sleep increases GH release
• Somatostatin will usually override GHRH

Question 12

GHRH and somatostatin

Answer 12

• GHRH source is hypothalamus, has been used to Rx slow growing children
• Very little GHRH is found in plasma
• Somatostatin is synthesized in the brain but also other tissues
• Particularly synthesized in pancreas where it suppresses insulin release

Question 13

Hyper secretion of GH

Answer 13

• Can result from pituitary tumors w/ activating mutations
• If hyper secretion occurs before bone epiphyses close (early life) leads to giantism
• Characterized by increased linear bone growth: long arms and legs
• If hyper secretion occurs after epiphyses close leads to acromegaly
• Characterized by bone growth (and thus large) fingers, toes, hands, feet, jaw, head
• To Rx this condition (besides surgery), can use drugs that target the GH receptor
• The receptor requires dimerization (w/ 1 molecule of GH) for any action, thus a GH analog (pegvisomant) that inhibits dimerization b/c it lacks 1 binding site will reduce GH activity

Question 14

Hyposecretion of GH

Answer 14

• Lack of GH release results in dwarfism if the deficit occurs in childhood
• Giving hGH can restore growth
• In adults lack of GH has no obvious signs
• GH resistance (laron syndrome) can cause the same problems in children and is due to inactivating mutations in GH receptor
• Cannot Rx them w/ hGH, must Rx w/ IGF1