Female Repro Physio (Day 1 - Menstrual Cycle)

Question 1

What are the 2 main androgens in women and what enzyme is known to catalyze it’s production?

Answer 1

Androstenedione and testosterone produced by CYP17 enzyme

Question 2

Define oligomenorrhea. What of amenorrhea. At what age would a woman’s fertility start to decrease?

Answer 2

Olidogmenorrhea - irregular menses (periods)
Amenorrhea - conditon without periods
After age 35, a woman’s fertility starts to decrease.

Question 3

What symptom is the most common intolerable symptom experienced by post-menopausal women? High levels of what hormone is associated with this?

Answer 3

Night sweats (hot flushes) are the most common symptom with post-menopausal women that is linked with high levels of Progesterone.

Question 4

What is the first half of the menstrual cycle? Describe its function in both the ovary and the uterus.

Answer 4

The Follicular phase (days 1-13) is the first half of the menstrual cycle that involves the increase in FSH (granulosa cell proliferation), the selection of a dominant follicle and the atresia of the non-selected follicles. In the uterus, this is known as the proliferative stage in which the endometrium thickens and becomes vascularized.

Question 5

What is the latter half of the menstrual cycle? Describe its function in both the ovary and the uterus.

Answer 5

The Luteal phase (days 15-28) is the second half of the menstrual cycle that occurs after ovulation at day 14. This leads to the thickening of the uterine lining (in secretory phase) that’s caused by secreted progesterone and E2 from the corpus luteum.

Question 6

The Graafian follicle before day 14 is known as the ___________ follicle. This is composed of an oocyte that is surrounded by _____-producing Granulosa cells and ______-producing Theca cells.

Answer 6

Preovulatory (Dominant) follicle; Estrogen is produced by FSH-stimulated, granulosa cells; Progesterone is produced by LH-stimulated, theca cells.

Question 7

Describe the role of the Hypothalamic-pituitary-ovarian axis in follicular steroidogenesis.

Answer 7

GnRH is secreted in a “pulsatile” manner which stimulates the carefully timed release of gonadotropins (LH and FSH). LH stimulates theca cells to secrete progesterone and FSH causes granulosa cells to secrete estrogen. These products provide negative and positive feedback on gonadotropin release.

Question 8

At low concentrations, Estrogen inhibits the secretion of ________.

Answer 8

Luteinizing hormone (LH) which explains the low, steady level of LH in the early follicular phase.

Question 9

What enzyme is known for catalyzing de novo steroidogenesis? What products does it help produce?

Answer 9

CYP11A catalyzes the steroidogenesis of Progestins (Pregnenolone and Progesterone)

Question 10

What enzyme is known to catalyze androgenesis? In what tissues can it be found and what products can be expected from its upregulation?

Answer 10

CYP17 enzyme catalyzes androgenesis to produce androgens (Androstenedione and Testosterone). This enzyme is found in both the adrenal gland and testis, in males.

Question 11

What enzyme is known to catalyze Estrogenesis? What products are expected?

Answer 11

CYP19, aromatase catalyzes estrogenesis to produces Estrogens (Estrone and Estradiol).

Question 12

During the early follicular phase, granulosa cells convert ______ from theca cells into ______.

Answer 12

A-dione (A4) is converted into estrogen by granulosa cells in ealry follicular phase.

Question 13

When theca cells are stimulated by LH, they secrete more ________ than testosterone. This works by the upregulation of _______ enzyme.

Answer 13

Androstenedione (A4) > T;

Catalyze by CYP17 which turns progesterone into A4 or DHEA.

Question 14

During the follicular phase, _______ binds receptors on granulosa cells, they secrete more ______ via the _______ enzyme.

Answer 14

FSH binds receptors on granulosa cells to secrete more Estradiol (E2) via CYP19 enzyme.

Question 15

Within the corpus luteum (during the luteal phase), LH binds to ________ cells to secrete more _________ than Estradiol (E2). What is the significance of this step in the uterus?

Answer 15

Granulosa lutein cells stimulated by LH to secrete Progesterone&raquo_space;> E2. This step prepares the uterus for implantation in early pregnancy.

Question 16

After gonadotropins bind to a receptor of a steroid producing cell, what rate-limiting step must occur for steroidogenesis to run to completion?

Answer 16

Cholesterol should be converted to Pregnenolone via CYP17 enzyme. C27 side chain is first cleaved to form the appropriate steroid hormone.

Question 17

List the 5 families of steroid hormones and some examples of each. Provide a mnemonic.

Answer 17

1. Progestins - Pregnenolone (P5) and Progesterone (P4)
2. Glucocorticoids - Cortisol
3. Androgens - Androstenedione (A4) and Testosterone (T)
4. Mineralocorticoid - Aldosterone
5. Estrogens - Estrone (E1) and Estradiol (E2)
   * *Mnemonic: “P-GAME”**

Question 18

From the recruitment of a follicular cohort, it takes ______ to reach ovulation. This phase from primordial to primary follicle is __________. After recruitment, events in the ovary are regulated by __________.

Answer 18

3 months to reach ovulation from recruitment; gonadotropin-independent
Post-ovulation events are regulated by FSH and LH

Question 19

Follicular ______ can occur at any stage during recruitment of folliculogenesis. This is the fate of ____ % of growing follicles.

Answer 19

Follicular Atresia;

98% of growing follicles

Question 20

Why are FSH levels held at a low level during the follicular phase of the menstrual cycle? (Provide 2 reasons)

Answer 20

1. Estradiol (E2) exerts a negative feedback at GnRH pulse generator (at level of hypothalamus).
2. Inhibin B (protein) from granulosa cells inhibit FSH secretion at the pituitary gland.

Question 21

What causes the change of negative feedback to positive feedback of Estradiol on the pulse-generator to stimulate gonadotropin secretion?

Answer 21

Low levels of Estradiol have a negative feedback role on GnRH pulsatility at first. This changes in the presence of HIGH levels of Estradiol that is conducive for estrogen production via a positive feedback mechanism. Gonadotropes produce activin, in an autocrine manner, to produce even more Estrogen.

Question 22

Negative feedback on the pulse generator is brought upon by ______ and ______. Whereas, positive feedback is brought up by _________ and ________.

Answer 22

Negative feedback = low E2 and Inhibin B;

Positive feedback = HIGH E2 and Activin

Question 23

What is the purpose of Inhibin A and how does it differ form Inhibin B?

Answer 23

Inhibin A is secreted by the Corpus Luteum to block the anterior pituitary’s function of secreting FSH. This is done in preparation for the next cycle because the smaller follicles die off since they cannot bind FSH with so few receptors. Inhibin B, on the other hand, is secreted by preovulatory Granulosa cells.

Question 24

Describe 3 events that occur during the onset of luteinization, as the follicle becomes the corpus luteum.

Answer 24

1. Granulosa cells (GC) that once expressed FSH, not also express LH receptors.
2. GC secrete Inhibin A to control lutein phase by lowering FSH secretion.
3. E2 and Progesterone is made to maintain normal lutein function.

Question 25

At the pre-ovulatory stage, _______ hormone levels are high due to the Dominant pre-ovulatory follicle. Just before ovulation, _______ hormone levels start to rise due to the ________, but peaks at the mid-luteal stage due to the ________.

Answer 25

Estrogen @ preovulatory stage is HIGH from the dominant follicle;
Progesterone starts to rise before ovulation due to the Dominant follicle but peaks at mid-luteal stage due to the Corpus Luteum.

Question 26

Progesterone is a ______ hormone that rises in levels during the ________ phase.

Answer 26

Thermogenic hormone that rises during the luteinizing phase. This increases basal body temperature

Question 27

Describe the negative feedback mechanism that Progesterone (P4) has on LH secretion. What is the clinical significance?

Answer 27

High levels of P4 stimulate progesterone receptor in hypothalamus that reduces the GnRH pulse frequency that profoundly lowers LH secretion much more than FSH secretion. This reduces ovulation via negative feedback. This is a reason why pregnant women do not go through cycles since the placenta is intact.

Question 28

Describe the negative feedback mechanism that Estrogen (E2) has on FSH secretion. What is the clinical significance?

Answer 28

High levels of E2 stimulates E2-receptor-alpha which reduces the GnRH pulse frequency that profoundly lowers FSH secretion compared to LH. This causes non-chosen follicles to die out via atresia. This explains why gonadotropins plummet during lutein phase or during pregnancy.

Question 29

High levels of progesterone during the mid-menstrual cycle down-regulates what 2 receptors? Why would it do that?

Answer 29

High P4 down-regulates ER and PR in order for the endometrial tissue to come out and prepare for menstrual shedding. This is in the case of no implantation.