Endocrinology of Pregnancy

Question 1

hCG and Pregnancy

Answer 1

o hCG (human chorionic gonadotropin) – produced by syncytiotrophoblasts cells of developing fetus few days after implantation
 Hormone used to determine pregnancy by pregnancy tests
 Similar structure to LH but slight difference in number of amino acids
 Bind to LH receptors on corpus luteum to maintain its function of secreting progesterone
o First 9 weeks – hCG maintains corpus luteum and thus progesterone production
o Week 9 – placenta takes over production and secretion of progesterone and estrogens
 Most important one is ESTRIOL (E3)
 Corpus luteum degenerates and hCG production decreases
o Progesterone = “pro gestational” hormone  inhibits contractions of smooth muscle in myometrium of uterus so that the embryo won’t be expelled
o Progesterone and estrogen levels continue to rise steadily throughout pregnancy

Question 2

Birth/Partruition

Answer 2

o # progesterone receptors on myometrium begin to decline and so does the effects of progesterone
o Estrogen levels begin to exceed progesterone (most of pregnancy progesterone is dominant)
 Estrogen begins to rise faster than progesterone starting 4 weeks before parturition
 Estrogen promotes uterine contractions
o Placenta produces its own CRH and the levels rise with the progression of development
 Stimulates fetal pituitary to release ACTH
 Fetal ACTH acts on fetal adrenal glands to produce DHEA-S
 DHEA-S leaves the fetus and is converted to estrogens (estriol) by aromatase enzyme found in placenta  helps makes estrogen levels greater than progesterone
o High estrogen levels increase activity of prostaglandin synthetase enzyme to pump out more prostaglandins (particularly PGF2alpha

Question 3

Factors that Cause Uterine Smooth Muscle Contractions

Answer 3

o Combination of estrogen + PGF2alpha irritate the smooth muscle of myometrium and begin uterus contractions (weak but strong enough to move fetus down uterus and stretch the cervix)
 Stress – causes release of catecholamines (epinephrine/norepinephrine) that cause smooth muscle contraction
 Stretch receptors in cervix cause maternal posterior pituitary to release oxytocin
• Stimulates strong contractions and moves delivery along

Question 4

Breast Development

Answer 4

o Pre-puberty – very little breast development and atrophic ducts
o Puberty – ovaries begin secreting estrogen which causes fat deposition and duct growth in breast
o During Pregnancy
 Progesterone causes lobulo-alveolar growth of ducts and accounts for large part of breast growth during this period
 High estrogen and progesterone levels suppress milk production by blocking prolactin
 High estrogen levels travel to anterior pituitary and stimulates proliferation of lactotroph cells to produce prolactin
• Anterior pituitary actually grows in size and becomes more metabolically active

Question 5

Milk Synthesis & Ejection

Answer 5

o Alveoli are functional units of mammary glands
o Baby suckling sends afferent signals to hypothalamus to release BOTH oxytocin and prolactin
 Afferent signal also inhibits arcuate nucleus production of dopamine
• Dopamine inhibits release of prolactin
• With dopamine inhibited, prolactin will be secreted
 Prolactin stimulates milk production by secretory cells surrounding the lumen
 Oxytocin – released by pituitary in response to baby suckling
• Causes smooth muscle cells outside of secretory cells to contract and secrete milk
o Removal of placenta results in no inhibition of prolactin’s effects
 Placenta is main source of high levels of progesterone/estrogen

Question 6

Prolactin’s Short Loop Negative Feedback

Answer 6

o End product of prolactin – milk – can’t feedback because it is released outside of body
o Prolactin travels to hypothalamus and trigger dopamine release to inhibit further prolactin release

Question 7

Nursing and Infertility

Answer 7

o Dopamine inhibits prolactin release and GnRH
o NO GnRH = no LH/FSH = infertile while nursing
o First few weeks postpartum there is robust amount of prolactin released
 Western Women - levels decrease over time
• More responsibilities outside of caring for their infant
 Underdeveloped Countries – continuous release of prolactin up to several years
• Fewer resources and therefore breast milk is infants main source of nutrition
• Will eventually cause large secretion of dopamine and prolonged suppression of GnRH and longer infertility time compared to Western Women
o Frequent suckling for long periods of time post-partum can be form of contraception
 If suckling does NOT occur the prolactin short loop feedback will degrade and dopamine will no longer inhibit GnRH

Question 8

Sheehan’s Syndrome Characteristics

Answer 8

–excess loss of blood (due to delivery); affects ANTERIOR pituitary gland
o Receives blood through VENOUS pituitary portal system  blood flow is not regulated well
o Highly metabolically active in pregnant women  requires more blood
o Panhypopituitarism – result of necrotic anterior pituitary due to lack of blood flow
 Loss of anterior pituitary hormones  ACTH, prolactin, GF, TSH, LH, FSH
• Loss of prolactin  no milk production
• Loss of ACTH no pubic hair; pale skin
o Loss of cortisol cause hypotension and Addison’s like complications
• Loss of LH and FSH  amenorrhea; infertility; decreased vaginal secretions; small uterus; small ovaries; atrophy of breasts
• Loss of TSH  small cardiac silhouette; hypothyroidism (fatigue, lethargic, cold intolerance)
• Loss of GH and prolactin  immune suppression

Question 9

Sheehan’s Syndrome Diagnosis

Answer 9

 Insulin test – give insulin to lower blood glucose; should cause increase in GH & ACTH
• Test ability of pituitary to synthesize those hormones
 Give TRH – should cause large increase in TSH
• Low TSH = few TSH cells still working
 SPECIFY time of day cortisol levels are measured  cortisol levels vary by time of day

Question 10

Sheehan’s Syndrome Treatment + extra characteristics

Answer 10

o More often in women who have births at home (less controlled environment than hospital)
o Men – can occur due to severe hemorrhage but not as common because anterior pituitary does not go under a state of high metabolic activity
o Posterior pituitary – UNAFFECTED due to ARTERIAL blood supply and hemodynamic forces that can regulate its blood supply
o TREATMENT: Hormone Replacement (in order of importance) – cortisol, TH, Estrogen/progesterone; androgens  give END hormone (NOT TSH/ACTH/LH/FSH