Female Repro phys review (Michels)

Question 1

FSH and LH levels across the lifespan of women

Answer 1

childhood– LH low
Puberty– LH begins pulsatile secretion
reproductive years– stays pulsatile
menopause– high levels and pulsatile

Question 2

Pituitary Ovary cross-talk

Answer 2

1. Corpus luteum dies, E and P levels fall
2. pituitary responds to falling E and P by increasing FSH secretion
3. FSH recruits a cohort of large antral follicles to enter rapid growth phase. Follicles secrete low amounts of E and inhibin
4. E and inhibin negatively feedback on FSH
5. declining FSH levels progressively cause atresia of all but 1 follicle– leading to selection of dominant follicle, which produces high levels of E
6. High E has positive feedback on gonadotropes– LH (and some FSH) surges
7. LH surge induces metabolic maturation, ovulation, and luteinization. The corpus luteum produces high P along with E and inhibin
8. High P, E and inhibin negatively feedback on LH and FSH, returning them to basal levels
9. The corpus luteum progressively becomes less sensitive to basal LH– dies if levels of LH-like activity (i.e. hCG) do not increase

Question 3

Stages of follicular development

Answer 3

primordial follicle - the ovarian reserve

(initiation)

primary follicle (cuboidal granulosa cells) –> secondary preantral follicle–> small antral follicle–> large, recruitable antral follicle–> dominant follicle at ovulation

Question 4

the gamete

Answer 4

oogonium (meiosis begins, but protein levels low) –>

primary oocyte arrested at prophase I (proteins synthesized; completes meiosis but high cAMP levels maintain arrest. . Completes meiosis and extrudes 1st polar body)–>

secondary oocyte arrests at metaphase II (completes meiosis at fertilization and extrudes 2nd polar body)–>

haploid ovum

Question 5

during follicular phase estrogen feeds back negatively on

Answer 5

LH and FSH

Question 6

Hormone production in follicular phase:

Answer 6

Thecal cells produce the androgen androstenedione (thecal cells have low levels of 17-hydroxysteroid dehydrogenase and therefore do not produce large amounts of testosterone)
In the second half of the follicular phase FSH induces the expression of LH receptors on mural granulosa cells- this allows mural granulosa cells to become response to both LH and FSH, retain CYP19 expression, and respond to the LH surge prior to ovulation (granulosa cells produce estradiol-17β)

Question 7

at the end of the follicular phase (going into luteal phase)

Answer 7

switch to positive feedback of estrogen on LH and FSH

Question 8

Periovulatory period-

Answer 8

time from the onset of the LH surge to the expulsion of the cumulus-oocyte complex (32-36 hours)

Question 9

Luteinization

Answer 9

mural granulosa cells now experience:

1. transient inhibition of CYP19 expression and estrogen production- turns off positive feedback
2. vascularization of the granulosa cells occurs- LHL and HDL cholesterol is now available for steroidogenesis
3. expression of StAR protein, CYP11A1 and 3-HSD (results in progesterone secretion)

Question 10

Corpus luteum formation

Answer 10

occurs after ovulation and serves as the source of progesterone (peaks in the mid-luteal phase). Luteal hormonal output is dependent on LH and both FSH and LH levels decline to basal levels in the luteal phase. The corpus luteum will die in 14 days unless rescued by HCG from the implanted embryo.

Question 11

The lifespan of the corpus luteum is

Answer 11

14 +/- 2 days unless rescued by HCG

Question 12

Hormone Effects on the Oviduct

Answer 12

Estrogen
\+ endosalpinx epithelial size
\+ blood flow
\+ oviduct specific glycoproteins
\+ ciliogenesis
\+ mucus, muscular tone

Progesterone
decreases epithelial size
\+ deciliation
decreases mucus
Relaxes muscular tone

Question 13

functions of the uterus

Answer 13

provide a site for attachment and implantation of the blastocyst
limit the invasiveness of the embryo
provide maternal side of placenta
grow and expand with growing fetus
provide muscular contractions to expel the fetus and placenta

Question 14

ovarian and endometrial cycles

Answer 14

ovarian follicular phase corresponds to proliferative endometrial phase

ovarian luteal phase corresponds to endometrial secretory phase

then menstrual phase

Question 15

The Cervix

Answer 15

Structure and function

• Highly elastic lamina propria
• Gateway to the upper female tract
• During the luteal phase passage of sperm is impeded due to changes in the endocervical canal

Hormonal regulation of cervical mucus

• Estrogen- stimulates production of a thin, watery, slightly alkaline mucus
• Progesterone- stimulates production of a scant, viscous, slightly acidic mucus (impediment to sperm passage)

Question 16

Estrogen/Progesterone Systemic Effects

Answer 16

Bone:
Estrogen promotes closure of epiphyseal plates and is an anabolic and calciotropic hormone

Liver:
Estrogens increase LDL receptor, HDL levels, and cortisol binding-protein, thyroid hormone-binding protein and sex hormone-binding protein

CV:
Estrogens cause vasodilation through NO synthesis

CNS:
Estrogens appear to be neuroprotective and progesterones regulate the set-point for thermoregulation

Question 17

Transport and Metabolism of Ovarian Steroids

Answer 17

Estrogen- 60% bound to sex-hormone binding globulin (SHBG), 20% bound to albumin, 20% in the free form
Progesterone- binds to cortisol-binding protein and albumin
Estrogens are metabolized in peripheral tissues, specifically adipose tissue

Question 18

Timeline of events during fertilization and implantation

Answer 18

ovulation- day 0
fertilization- 1
blastocyst enters uterine cavity- 4 days
implantation- 5 days
trophoblast forms and attaches to endometrium- 6 days
trophoblast begins to secrete HCG- 8 days
HCG rescues corpus luteum- 10 days

Question 19

Hormones of Pregnancy

Answer 19

The duration of pregnancy is counted from the date of the last menstrual cycle
40 weeks total or 38 weeks from ovulation

1st trimester
HCG rescues corpus luteum and stimulates corpus luteal production of estrogen and progesterone

2nd and 3rd trimester
The placenta in combination with the mother and fetus take over production of progesterone and estrogen

Question 20

hormone levels during pregnancy

Answer 20

1st trimester- HCG high. The hormone of morning sickness

prolacting, progesterone and etriol rise slowly throughout the pregnancy

Question 21

Limitations of the placenta

Answer 21

Cannot make adequate cholesterol
Lacks enzymes for estrone and estradiol
Lacks enzyme for estriol

Question 22

Mother- needs, contributes, lacks

Answer 22

needs: progesterone, estrone, estradiol, estriol

contributes- LDL cholesterol

lacks- adequate synthetic capacity for progesterone and estrogens

Question 23

Placenta- contributes, lacks

Answer 23

contributes 3 beta-hydroxysteroid dehydrogenase aromatase (P-450 arom)

lacks- adequate cholesterol synthesizing capacity
17-alpha hydroxylase
17,20 desmolase
16 alpha hydroxylase
(those guys are used to make estradiol and estriol)

Question 24

Fetus- contributes, lacks

Answer 24

contributes the 17 alpha hydroxylase, 17,20 desmolase, and 16 alpha hydroxylase

needs 3 beta hydroxysteroid dehydrogenase aromatase

Question 25

Hormone Synthesis During Pregnancy

Answer 25

mom sends cholesterol to placenta for progesterone synthesis–> both mom and baby

and also for prenenolone–> fetus–> 16OHDHEA-sulfate–> back to the placenta to make estriol for mom

Question 26

Human Placental Lactogen (hPL)

Answer 26

Also referred to as human chorionic somatomammotropin (hCS)
Structurally similar to GH and PRL
Detectable in maternal serum at 3 weeks- increases thereafter (directly proportional to size of placenta)

Antagonistic action to insulin → diabetogenic effect
Increases glucose availability for the fetus
Simulates mammary growth and development

Question 27

Maternal Endocrine Changes

Answer 27

Pituitary:
2X increase in size
ADH set-point lowered

Adrenal:
Cortisol and aldosterone levels rise
Estrogen stimulates activity of the renin-angiotensin-aldosterone system

Thyroid:
Total T4 and T3 increase but free T4 is normal
TSH levels decrease in the first trimester

Question 28

Cardiovascular Changes

during pregnancy

Answer 28

↑Vascular volume
↓Peripheral resistance
↑Stroke volume
↑Heart rate
↑Contractility
↑Cardiac output

Question 29

Respiratory Changes

during pregnancy

Answer 29

↑Minute volume
↑Tidal volume
↓PCO2
↓FRC
↓IRV
Respiratory alkalosis

Question 30

Renal Changes

Answer 30

↑ADH, renin, angiotensin II, aldosterone

increased GFR

Question 31

Parturition- stages of labor and initiation of parturition

Answer 31

Stages of labor

1. Strong uterine contractions
2. Delivery of the fetus
3. Delivery of the placenta

Initiation of parturition

• Placental CRH
• Estrogen
• Oxytocin
• Prostaglandins
• Uterine size

Question 32

Endocrine Changes after Parturition

Answer 32

Estrogens and progesterone drop

prolactin begins intermittent spiking during nursing

Question 33

neuroendocrine reflex in lactation

Answer 33

suckling at nipple–>

• decreases dopamine from parvicellular neurons and
• increases oxytocin from the pars nervosa (via magnocellular neurons)

dopamine decrease leads to increased prolactin which also decreases GnRH–> decreased LH and FSH–> lactational amenorrhea