Week 1: female reproductive physiology

Question 1

Describe the hypothalamic pituitary gonadal axis

Answer 1

• hypothalamus releases GnRH
• anterior pituitary releases LH and FSH
• LH and FSH into systemic circulation. Act on gonads
• stimulates ovaries to produce steroid hormone and gamete maturation. LH stimulates steroid hormone production, while FSH is more important for production of gametes.

Question 2

Describe hormone negative feedback in female reproductive system and pulsatile secretion.

Answer 2

• LH is used as proxy for GnRH secretion since it can’t easily be measured
• high levels of steroid hormone feedback to inhibit GnRh and LH secretion
• There is pulsatile release of GnRH and LH. In the absence of negative feedback from steroid hormone, the frequency of the pulses increases, not the amplitude.
• when given continuous instead of pulsatile GnRH, LH/FSH secretion is inhibited.

Question 3

Pharmacological control of LH and FSH release

Answer 3

• Giving GnRH agonist in pulsatile way: increases FSH, LH and fertility
• GnFH agonist at constant concentration inhibits FSH, LH release. As does giving GnRH antagonist. Might be useful in men with androgen dependent prostate cancer or women undergoing assistive reproductive tech.

Question 4

Features of steroid synthesis: androgens and estrogens

Answer 4

1. Estrogens are made from androgens. Testosterone can be converted to estradiol.
   - DHT is also an androgen, converted from testosterone, but binds with higher affinity and can’t be converted to estrogen
2. Progesterone is made in an early step in steroid synthesis. Produced in prep of pregnancy and during pregnancy.

Question 5

Menstrual cycle-overview

Answer 5

1. Follicular phase: days 1-13
   - Primordial follicle: oocyte surrounded by single layer of granulosa cells
   - a couple develop into primary follicles. Follicle grows, recruits thecal cells. Increased estradiol secretion.
   - Early antrum formation: fluid build up
   - graafian follicle (antral follicle)
2. Ovulation: LH surge. oocyte ruptures out of ovary, takes some granolas cells with it, but most cells stay behind
3. Luteal phase: day 15-28
   - formation of corpus lute from ovulated follicle. Secretion of progesterone and estrogen from CL.

Question 6

Steroidogenesis in ovaries

Answer 6

1. LH and theca cells
   - thecal cells made androgens in response to LH
   - LH binds, and adenylate cyclase is activated via G protein. cAMP activates protein kinase A
2. FSH and granulosa cells
   - androgens diffuse across to granulosa cells, aromatized to estrogens under influence of FSH
   - Estrogen further stimulates FSH receptors, promoting more estrogen synthesis

Question 7

Hormone changes during menstrual cycle

Answer 7

1. Follicular phase
   - increase estrogen production, under influence of LH/FSH
   - negative feedback by low estrogen and Inhibin, stimulated by FSH release. Inhibits FSH secretion.
2. Ovulatory phase
   - positive feedback with high levels of estrogen! leads to positive feedback to produce more GnRH and LH
   - LH surge leads to ovulation.
   - stops with release of oocyte
3. Luteal phase
   - CL secretes progesterone and estrogen. peaks 8 days after surge, declines by 12 days post surge.
   - negative feedback by progesterone on hypothalamus and anterior pit on LH and FSH release.

Question 8

Reproductive effects of estrogen in females

Answer 8

• most effects on uterus since exposed to higher levels of estrogen due to blood supply from ovary going to endometrium
  1. growth an proliferation of epithelial cells of endometrium
  2. myometrium: estradiol stimulates uterine contractions. Progesterone inhibits to facilitate implantation.
  3. Oviducts: estradiol stimulates cilia in oviduct and contractility of oviduct . Progesterone sitmulates secretions. Promotes transport of gametes, fertilization.
  4. estradiol alter cervical mucus, so sperm more able to penetrate cervix at ovulation. Increases Spinnbarkeit-stretchyness of mucus.
  5. estrogen thickens mucosa lining in vagina and promotes fluid secretion during sex

Question 9

Systemic effects of ovarian steroids

Answer 9

• increase in basal body temperature due to progesterone.
• estrogen+androgen stimulates libido
• affects fat distribution, metabolism, bone turnover, secondary sex characteristics, sex behavior