Female Reproductive Physiology (Week 7--Wayne) Flashcards
3 phases of the ovarian (menstrual) cycle
1) Follicular phase (corresponds to proliferative phase of menstrual cycle)
2) Ovulatory phase
3) Luteal phase (corresponds to secretory phase of menstrual cycle)
Follicular phase
Growth of ovarian follicle
Estradiol secretion from ovary
Increased pulse frequency of GnRH secretion
Corresponds to proliferative phase of menstrual cycle
Ovulatory phase
LH surge leads to ovulation
Luteal phase
Formation of corpus luteum (CL) from ovulated follicle
Increased progesterone (and estradiol) secretion from CL
Decreased pulse frequency of GnRH secretion
Corresponds to secretory phase of menstrual cycle
3 phases of follicular phase
1) Pre-antral phase (early): primary oocyte grows; granulosa cells proliferate; granulosa cells develop estrogen and FSH receptors; thecal cells with receptors for LH develop; independent of LH and FSH (this phase happens even without LH and FSH)
2) Antral phase (mid): many follicles undergo atresia and death of oocyte; increased synthesis and secretion of estradiol and androgen; conversion of preantral to antral (Graafian) follicle; estradiol and FSH cause LH receptors to develop on granulosa cells (critical for next phase); estradiol switches from negative to positive feedback here
3) Preovulatory phase (late): LH stimulates synthesis and secretion of progesterone and prostaglandins (from granulosa cells (this is why LH on granulosa cells so important for ovulation!) and thecal cells!); LH surge stimulates ovulation and formation of CL
Steroidogenesis during early antral phase of follicular phase (2 cell hypothesis)
Thecal cells synthesize androstenedione from cholesterol (stimulated by LH)
Granulosa cells get androstenedione and convert it to estradiol via aromatase (stimulated by FSH)
Granulosa cells also secrete estrogen and induce themselves to proliferate and synthesize more FSH and thus more estrogen (also local positive feedback during follicular phase)
How do you explain the difference in LH pulse frequency between follicular and luteal phases?
In follicular phase, there is suppression of normal estradiol negative feedback (positive feedback) so get high frequency of LH pulse secretion
In luteal phase, have negative feedback of estradiol so get low frequency of LH pulse secretion
Note: FSH affected same way as LH
What is it that matters, the LH pulse frequency or pulse amplitude?
Pulse frequency is what matters!
High pulse frequency means high secretion
Note: inverse relationship between pulse frequency and pulse amplitude
What triggers the LH surge (which in turn triggers ovulation)?
Increase in GnRH pulse frequency (GnRH surge)
But estradiol must reach its threshold level to cause this increase in GnRH (positive feedback still remember)
What is menopause?
Progressive failure of reproductive system
Occurs between 45 and 55
Due to failure of ovarian function: number of oocytes down to 10,000, remaining follicles are less responsive to GnRH because of degeneration of granulosa and theca cells
During the luteal phase, what are estrogen and progesterone doing?
“Luteinization” of the follicle means LH surge caused ovulation which creates the CL
During luteal phase E and P secreted by CL have negative feedback on HPG axis to decrease pulse frequency of GnRH
This means LH and FSH secretion are low also (good because don’t want follicular growth because don’t want double ovulation!)
Also, E and P from CL prepare the uterus/endometrium for implantation/maintenance of pregnancy
What happens if there is no signal for pregnancy?
CL dies because needs LH to sustain it and LH declines after its surge –> E and P were secreted by CL, so now no more E and P –> since E and P were what supported endometrum, now the endometruim sloughs off
Can you prevent death of CL with continuous treatment with LH?
No, but we don’t know why not!
hCG is what maintains the CL if a woman becomes pregnant, and hCG actually binds the LH receptor, but we still can’t use LH itself to maintain CL
What do E and P do during the follicular phase?
At first there is no E and P because the CL died, so GnRH, LH, FSH are high because no negative feedback fro E and P
A weird thing happens in humans where the brain switches from having E do negative feedback to having it do POSITIVE feedback –> as E increases slowly, it causes an INCREASE in LH and FSH and this stimulates the ovarian follicle
What is the “winner” follicle called?
Graffian, dominant, or mature follicle is the one that matures enough to allow ovulation
It’s the one that expresses the most FSH receptors
Why is the follicular phase all about estrogen’s positive feedback?
There is distant positive feedback on the HPG axis (increase GnRH secretion, increase LH (and FSH) secretion)
There is local positive feedback on the granulosa cells themselves (estradiol secreted by granulosa cells themselves causes proliferation of themselves and more expression of FSH receptors on them to create aromatase to make even more estradiol)
What physically allows for ovulation?
The follicular wall becomes thinner and ruptures at the stigma about 16 hours after peak of LH surge and causes follicular fluid to pour out, carrying oocyte with it (not an explosion, no change in antral pressure!)
Proteolytic enzymes released from follicular cells cause thinning of follicular wall (possibly prostaglandins and progesterone involved in this)
When is the peak E and P secretion by the CL during the luteal phase?
8 days after LH surge (day 8 of luteal phase)
Then declines to baseline at day 12 of luteal phase
