Menstrual Cycle

Question 1

2 phases of menstrual cycle? For ovary/uterus?

Which phase has a more variable length?

Answer 1

1st phase: Follicular/proliferative (more variable)

2nd phase: Luteal/secretory

Question 2

What does the hypothalamus produce in the HPO axis?

Answer 2

GnRH

Question 3

What’s the difference in secretion patterns of GnRH between the follicular/proliferative vs. luteal/secretory phase?

Answer 3

Follicular: Higher frequency and LOWER amplitude
Luteal: Lower frequency and HIGHER amplitude

Question 4

What are the gonadotropins made by the anterior pituitary?

Answer 4

FSH and LH

Question 5

What kind of molecules are FSH and LH? What 2 other molecules have very similar structures?

Answer 5

Glycosylated polypeptides composed of alpha and beta subunits (the beta unit varies).
hCG and TSH are similar.

Question 6

2 essential hormones for reproduction made by the ovary?

Answer 6

1) Estradiol
2) Progesterone
(but other stuff is made)

Question 7

What, simply, does FSH do?

Answer 7

Simulates follicles to start maturing in the race to become the dominant follicle.

Question 8

What does the FSH levels vs. time look like?

Answer 8

Elevated early in menstrual cycle, dips, then spikes sharply with the LH surge just prior to ovulation.

Question 9

What does FSH do to specific cells / endocrine activity / etc.? (3 things)

Answer 9

1) Stimulates granulosa cell proliferation.
2) Stimulates aromatase in granulosa cells for androgens -> estrogens
3) Upregulates FSH and LH receptors.

Question 10

What enzyme converts androgens to estrogens? In what cell does this conversion occur? But WHERE are the androgens made?

Answer 10

Aromatase

• Androgens made by theca cells
• Androgens –> Estrogen in the granulosa cells

Question 11

Important: What’s the relationship between FSH and estradiol? (Neg feedback to Pos feedback switch)

Answer 11

FSH increases estradiol levels due to granulosa proliferation / aromatase expression–> leads to rise of estradiol
Estradiol initially has negative feedback on FSH.
Once estradiol level is high enough, has positive feedback on FSH -> FSH and LH surge (via increased GnRH pulse frequency).

This switch happens the DAY before ovulation

Question 12

When do serum estradiol levels peak?

Answer 12

1 day before ovulation.

Question 13

3 effects of the LH surge?

Answer 13

1) Release of oocyte from follicle via enzymes(36hrs after surge begins).
2) Leads to luteinization of granulosa cells -> increased progesterone production (THIS is why you see a sharp drop in estradiol at the time of the LH surge and the beginning rise of progesterone)
3) Resumption of meiosis -> release of 1st polar body.

Question 14

When is meiosis complete in the oocyte/ovum?

Answer 14

Not until after fertilization.

Question 15

Contrast the activity of estrogen and progesterone on the endometrium.

Answer 15

Estrogen: promotes proliferation, growth, prominent mitoses, glands lined with low columnar epithelium
Progesterone: Limits growth/mitosis, increases tortuosity/coiling of glands and vessels, promotes secretion of glycoproteins and peptides (getting ready for embryo implantation)
(Note you can’t give estrogen to a woman with a uterus without giving progestin, as it increases risk for endometrial cancer)

Question 16

What cellular process prepares the endometrium in the luteal phase for implantation? What does it look like histologically?

Answer 16

Decidualization: spindle-shaped stromal fibroblasts become plump secretory decidual cells

Question 17

What precipitates menstruation?

Answer 17

Corpus luteum degenerates after 14d- shelf life!
Loss of estrogen and progesterone -> loss of endometrium.
Loss of NEG feedback on FSH–> FSH rises again

Question 18

Why does FSH come back up after menstruation?

Answer 18

Because the estrogen’s gone, FSH is no longer being suppressed via negative feedback.

Question 19

How does pregnancy prevent menstruation?

Answer 19

hCG from fetus makes corpus luteum persist, making estrogen and progesterone until the placenta takes over.

Question 20

Which cells make Inhibin?

Answer 20

Granulosa cells

Question 21

3 actions of Inhibin?

Answer 21

1) Blocks FSH synth and release from pituitary. (and decreases GnRH receptors)
2) Increases LH receptors on theca cells.
3) Competes for activin receptor and inactivates activin.

Question 22

Where is Activin made?

Answer 22

Ovary and pituitary

Question 23

2 actions of Activin in the pituitary?

Answer 23

1) Increases FSH secretion.

2) Increases GnRH receptor levels.

Question 24

3 action of Activin in the follicle?

Answer 24

1) Promotes granulosa proliferation.
2) Increases FSH receptor levels.
3) Enhances ability of FSH to induce aromatase and androgen production.

Question 25

What is a normal cycle length?

Answer 25

24-35 days

Question 26

Explain the HPO pathway via it’s anatomical route

Answer 26

1) Hypothalamic neurons secrete GnRH into primary capillary plexus
2) GnRH travels through PORTAL vein to the pituitary–> stimulates release of FSH and LH
3) Anterior pituitary secretes the FSH and LH into secondary capillary plexus–> goes out into system circulation

Question 27

What part of follicular development is hormone INDEPENDENT? What happens in this period?

Answer 27

• Early development of primordial–> primary–> secondary follicle does NOT require hormones (i.e. is happening BEFORE puberty)
• Oocyte grows a little bit
• Granulosa cells proliferate
• Development of theca interna cells

Question 28

What part of follicular development is gonadotropin dependent (FSH dependent)?

Answer 28

• Needed to get BEYOND secondary oocyte
• Preantral–. Antral– Selected— Preovulatory
• Group of follicles grow–> by day 8 one follicle becomes dominant and the rest atrophy

Question 29

What exactly are activin and inhibin?

Answer 29

2nd level of hormonal regulation

• Are part of TGF- B superfamily
• Inhibin–> inhibits FSH
• Activin–> activates FSH