Female reproductive physiology Flashcards
1
Q
Pulsatile release of GnRH, LH, and FSH
A
- LH and FSH are released in pulsatile fashion, in response to pulses of GnRH from hypothalamus
- Pulses of LH, FSH are required for full sexual maturity and function
- If release of GnRH is continuous and not pulsatile then LH and FSH release falls and sexual dysfxn (infertility) occurs (due to down-regulation of GnRH receptors)
2
Q
Generation of steroids due to gonadotropin stimulation
A
- Process is similar in males and females: LH (and FSH in females) bind to their receptors in the gonads and activate AC
- Increase in cAMP leads to synthesis of steroid hormones from cholesterol and immediate release of these hormones into circulation
- The hormones are not pre-made and stored, they are made and released on command by LH (and FSH in females)
- In females the steroid hormones are estrogen (primarily estradiol, E2) and progesterone (P) which are made by the cells that surround and support the developing oocyte (oocyte + support cells = follicle)
3
Q
Steroid hormone synthesis
A
- Androgens (androstenedione) are precursor to E2, and thus women make T so they can convert it to E2 via aromatase nz
- Progesterone is earlier on in the synthesis pathway (not made from T)
- T can also be acted on by 5 alpha reductase to be converted to DHT, an androgen that has a much higher affinity for the androgen receptor than T
- DHT cannot be converted to E2 and is important for male genitalia formation
- Steroids act on receptors in cytoplasm and the complex is translocated to nucleus to alter gene expression
- These effects are long-term but there may also be short-term effects from steroid hormones as well
4
Q
Follicular development throughout menstrual cycle 1
A
- Primordial follicles are quiescent cells that may be activated to primary follicles (mech unknown)
- These primary follicles begin to grow under the influence of FSH/E2 from days 1-13 of the cycle
- The primary follicle develops into an early antrum follicle, where the oocyte is surrounded by granulosa cells, then a basement membrane, then theca cells
- These surrounding granulosa cells produce large quantities of E2 in response to gonadotropin release from ant pit (particularly FSH)
- Gonadotrophs are not required for primary follicle to develop from quiescent follicles (mech unknown), but FSH is required for further development of primary follicles
5
Q
Follicular development throughout menstrual cycle 2
A
- Eventually some follicles develop into graafian follicles, which are large and contain fluid w/ E2
- The high levels of E2 leads to growth of endometrium in uterus in preparation for the oocyte
- On day 14 there is an LH surge from the ant pit leading to follicular rupture and release of oocyte (ovulation)
- The luteal phase (days 15-28) of the ovary demonstrates corpus luteum (remnants of the theca/granulosa cells form follicle) formation, which releases P and E2 at high levels
- If fertilization and implantation do not occur there corpus luteum regresses (no hormone signal of implantation) and part of the endometrium is shed (menses)
6
Q
Two-cell process of steroidogenesis in females
A
- Androstenedione (androgen) is produced by theca cells from cholesterol under the influence of LH binding and cAMP formation
- Granulosa cells take the androstenedione and aromatize it to E2 under the influence of FSH binding to granulosa cells
- Granulosa cells contain E2 receptors, which increase synthesis of FSH receptors and stimulates cellular proliferation
- Thus there is local positive feedback of E2 on E2 formation
7
Q
28 day menstrual cycle: follicular and uterine phases 1
A
- Follicular phase of ovary corresponds to menstrual and proliferative phases in uterus, and the luteal phase of the ovary corresponds to the secretory phase of the uterus
- The cycle starts are onset of menses from the previous cycle
- Part of the endometrium is sloughed off due to degeneration of corpus luteum (CL)-> fall of E2/P
- Since E2/P levels are lowest here, the levels of GnRH-> FSH/LH begin to rise due to lack of negative feedback
- This causes development of follicles (starts at day 1: beginning of menstrual phase), and most follicles that develop during this time become atretic, while only one dominant one (usually) will ovulate
8
Q
28 day menstrual cycle: follicular and uterine phases 2
A
- Around day 4-5 the levels of E2 get to the point where the endometrium begins to grow again (proliferative phase)
- Around day 14 the E2 levels are so high (due to the graafian follicle about to rupture) that there is conversion from E2 negative feedback on the hypothal/ant pit to positive feedback in these regions
- This leads to the LH surge at day 14 causing follicular rupture and ovulation
9
Q
28 day menstrual cycle: follicular and uterine phases 3
A
- Ovulation leads to a quick drop in E2 levels, allowing for resumption of negative feedback of E2 on hypothal/ant pit
- This marks the transition to luteal phase/secretory phase, where P/E2 levels remain elevated (from CL) to stimulate growth and secretion w/in the endometrium
- There is very low FSH/LH during this phase due to negative feedback of E2/P on hypothal/ant pit
- As CL degenerates (when no implantation) around day 28 the E2/P levels fall and FSH/LH levels rise and the cycle begins again
10
Q
Inhibin
A
- A hormone made by granulosa cells that seems to be a primary inhibitor of FSH secretion by the ant pit
- Inhibin is released during follicular phase (under control of FSH) as the follicle grows and decreases FSH release from ant pit and GnRH release from hypothal (along w/ E2 feedback)
- This causes atresia in all but the dominant follicle
11
Q
LH surge
A
- Happens when E2 levels become sufficiently high to change from negative feedback to positive feedback in ant pit/hypothal
- LH surge is essential for ovulation and oocyte maturation (is required for fertilization)
- When ovulation occurs there is a sharp drop in E2 (from destruction of follicle) and this returns E2 to negative feedback on the ant pit/hypothal
12
Q
Variability in cycles
A
- Luteal phase is always 14 days
- Differences in the follicular phase is almost always what makes menstrual cycle length variable
13
Q
Systemic effects of ovarian steroids 1
A
- Uterus: E2 stimulates growth of endometrium, spontaneous contraction of myometrium. P stimulates endometrium to provide nutrients for embryo and inhibits contraction of myometrium to allow for implantation
- In oviducts: E2 stimulates cilia movement and P stimulates secretions into lumen for transport of gametes
- Cause alterations in cervical mucus, leading to higher volume of mucus production and higher sperm penetration near ovulation (when E2 levels are at max)
- P causes hardening of cervix during luteal phase, preventing sperm penetration
14
Q
Systemic effects of ovarian steroids 2
A
- E2 promotes fluid secretion of vagina and thickens mucosal lining
- E2 has effects on bone density (decreases bone resorption), secondary sex characteristics development (breasts), sexual behavior
- E2 promote receptivity, but androgens promote proceptivity (seeking sex)
- Androgens cause growth of pubic hair in both men and women
