Lecture 5-Hypothalamus And Pituitary 2

Question 1

Summarize the effects of GH deficiency

Answer 1

• In most cases due to panhypopituitarism or lack of GH or resistance to GH
• If it occurs in children results in dwarfism
• Laron - type dwarfs have defective GH receptors
• In adults no known effects – known to increase vitality & lean muscle mass in elderly if administered GH
• Growth hormone is species specific

Question 2

What is panhypopituitarism?

Answer 2

• Is due to deficiency of all pituitary hormones
• May be congenital or occur later in life due to infarction as in Sheehan’s syndrome due to postpartum hemorrhage
• In children leads to dwarfism, hypogonadism & mental retardation
• In adults it has 3 major effects
– hypothyroidism - decreased sexual hormones – decreased glucocorticoids

Question 3

What are the effect of pituitary stalk injuries?

Answer 3

• diabetes insipidus
• panhypopituitarism
• hyperprolactinemia

Question 4

What is the structure of prolactin?

Answer 4

Is 199 AA & produced in the anterior pituitary in the anterior pituitary , and stored in granules

Similar in structure to GH but doesn’t have growth hormone like effects

Question 5

What is the half life of prolactin?

Answer 5

20 minutes

Question 6

Is prolactin gender specific?

Answer 6

No

Question 7

What are the functions of prolactin?

Answer 7

• Main function is breast development & milk
production, but not ejection of milk
• It initiates & maintains of milk production
• Inhibits ovulation in lactating female suppressing GnRH synthesis & release

Question 8

Explain the regulation of prolactin

Answer 8

Hypothalamus releases dopamine which inhibits PIF

Anterior pituitary release of prolactin is suppressed

Estradiol inhibits dopamine action in hypothalamus

TRH stimulates anterior pituitary

Estradiol sensitizes anterior pituitary to TRH

These increase prolactin

Question 9

What is the mechanism of action of dopamine on lactotrophs ?

Answer 9

Dopamine binds to receptor and decreased cAMP and via PKA decreasing

Prevents calcium influx

Decreased Ca2+inhibit the exocytosis of PRL

Question 10

What is the mechanism of action in target tissues?

Answer 10

Prolactin binds to receptors

Increase in tyrosine kinase, causing modulation of gene expression, these cause prolactin effects

Question 11

What are the effects of prolactin?

Answer 11

• Breast differentiation
• Duct proliferation and branching
• Glandular tissue development
• Milk protein synthesis
• Lactogenic enzyme synthesis

Mammary gland development
Milk production

Question 12

What are the most common pituitary gland?

Answer 12

Prolactinomas are the most common tumors (26%) in adults causes
- usually microadenomas < 10 mm
- macroadenomas if > 15mm cause
bitemporal hemianopsia

Question 13

What are the disorders of prolactin imbalance?

Answer 13

• Excess secretion of hormone causes
- galactorrhea
- decreased libido
- decreased ovulation & spermatogenesis
by inhibiting GnRH
• Dopamine agonist, bromocriptine can be used to treat excess prolactin secretion
• Deficiency results in failure to lactate

Question 14

What are the posterior pituitary hormones?

Answer 14

Oxytocin

Antidiuretic hormones (ADH, AVP or Vasopressin)

Both are 9 AA peptides with a minor difference

Both synthesized from a prohormone containing a larger peptide containing neurophysins with a slight difference
Diabetes Insipidus is associated with mutations in neurophysins

Question 15

What are the effects of ADH secretion?

Answer 15

• Increased ECF osmolarity via osmoreceptors

- Decreased ECF volume via baroreceptors

Question 16

What is the mechanism of action on ADH- kidney (collecting duct)?

Answer 16

ADH binds to V2 receptor

Which increased cAMP which not only increases AQP2 production, but also vesicles containing vesicles containing AQP2

AQP2 sent to membrane

Question 17

What is the mechanism of action on blood vessels?

Answer 17

ADH binds to V1 receptors

-Increased IP3 & DAG and leads to increased CA2+ causing contraction for vascular smooth muscle cell

Question 18

Explain the 2 types of diabetes insipidus

Answer 18

Central
- decreased levels of ADH - Lesions in CNS
- treated with ADH
analogue dDAVP

Nephrogenic
-increased levels of ADH
- due to defects in V2 receptor,
Gs protein or adenylyl cyclase, hypercalcemia & drugs such
as lithium

Question 19

Differentiate syndrome of inappropriate ADH or SIADH

Answer 19

• SIADH is&raquo_space; ADH secreted by tumor (such as oat cell Ca for the lung)
• Results in
-increased ADH secretion H2O retention
-increasedurinary concentration
-decreased serum osmolarity
• Treatment is with ADH antagonist such as
demeclocycline or water restriction

Question 20

What are the reasons for releasing oxytocin ?

Answer 20

Nursing a baby

Pressure against cervix

Question 21

What is the mechanism of action of oxytocin on target cells?

Answer 21

Increased IP3 & DAG leads to increased Ca2+ leads to contraction of smooth muscle cell

Question 22

What are the effects and causes of oxytocin release ?

Answer 22

Causes fear, pain, noise, fever—> ocytocin release causes contraction of myoepithelial cells also uterine contraction

Sucking of lactating breast and stretch of cervix end of pregnancy stimulates oxytocin release