Menstrual Cycle Flashcards
1) Understand each component of HPO axis, the structure and functio of the hormones they produce 2) Understand follicular developmen in the ovary and hormone production by the ovarian follicle 3) Know the changes occurring in the endometrium over the cycle 4) Understand the regulation of the HPO axis through negative and positive feedback
2 phases of menstrual cycle? For ovary/uterus?
Which phase has a more variable length?
1st phase: Follicular/proliferative (more variable)
2nd phase: Luteal/secretory
What does the hypothalamus produce in the HPO axis?
GnRH
What’s the difference in secretion patterns of GnRH between the follicular/proliferative vs. luteal/secretory phase?
Follicular: Higher frequency and LOWER amplitude
Luteal: Lower frequency and HIGHER amplitude
What are the gonadotropins made by the anterior pituitary?
FSH and LH
What kind of molecules are FSH and LH? What 2 other molecules have very similar structures?
Glycosylated polypeptides composed of alpha and beta subunits (the beta unit varies).
hCG and TSH are similar.
2 essential hormones for reproduction made by the ovary?
1) Estradiol
2) Progesterone
(but other stuff is made)
What, simply, does FSH do?
Simulates follicles to start maturing in the race to become the dominant follicle.
What does the FSH levels vs. time look like?
Elevated early in menstrual cycle, dips, then spikes sharply with the LH surge just prior to ovulation.
What does FSH do to specific cells / endocrine activity / etc.? (3 things)
1) Stimulates granulosa cell proliferation.
2) Stimulates aromatase in granulosa cells for androgens -> estrogens
3) Upregulates FSH and LH receptors.
What enzyme converts androgens to estrogens? In what cell does this conversion occur? But WHERE are the androgens made?
Aromatase
- Androgens made by theca cells
- Androgens –> Estrogen in the granulosa cells
Important: What’s the relationship between FSH and estradiol? (Neg feedback to Pos feedback switch)
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
When do serum estradiol levels peak?
1 day before ovulation.
3 effects of the LH surge?
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.
When is meiosis complete in the oocyte/ovum?
Not until after fertilization.
Contrast the activity of estrogen and progesterone on the endometrium.
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)
What cellular process prepares the endometrium in the luteal phase for implantation? What does it look like histologically?
Decidualization: spindle-shaped stromal fibroblasts become plump secretory decidual cells
What precipitates menstruation?
Corpus luteum degenerates after 14d- shelf life!
Loss of estrogen and progesterone -> loss of endometrium.
Loss of NEG feedback on FSH–> FSH rises again
Why does FSH come back up after menstruation?
Because the estrogen’s gone, FSH is no longer being suppressed via negative feedback.
How does pregnancy prevent menstruation?
hCG from fetus makes corpus luteum persist, making estrogen and progesterone until the placenta takes over.
Which cells make Inhibin?
Granulosa cells
3 actions of Inhibin?
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.
Where is Activin made?
Ovary and pituitary
2 actions of Activin in the pituitary?
1) Increases FSH secretion.
2) Increases GnRH receptor levels.
3 action of Activin in the follicle?
1) Promotes granulosa proliferation.
2) Increases FSH receptor levels.
3) Enhances ability of FSH to induce aromatase and androgen production.
What is a normal cycle length?
24-35 days
Explain the HPO pathway via it’s anatomical route
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
What part of follicular development is hormone INDEPENDENT? What happens in this period?
- 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
What part of follicular development is gonadotropin dependent (FSH dependent)?
- 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
What exactly are activin and inhibin?
2nd level of hormonal regulation
- Are part of TGF- B superfamily
- Inhibin–> inhibits FSH
- Activin–> activates FSH