Menstrual cycle Flashcards
Regulation of sex steroid production
GnRH from hypothalamus - cyclic release in adulthood
stimulates release of LH & FSH from anterior pituitary, stimulate ovary
ovaries produce steroids (estradiol from granulosa; progesterone from luteal)
Theca cells
produce androstenedione
Granulosa cells
produce estrogens (mostly estradiol)
Postovulatory changes to cells
Theca and granulosa cells become luteal cells
–> produce estrogen and progesterone
Primary follicles over life
undergo apoptosis from birth onwards
2 mil primordial follicles at birth
400k remain at puberty
average woman will ovulate 500 times
Ovarian component f menstraul cycle
maturing an oocyte and its ovulation
follicular phase is variable, luteal is fixed: 12-14 d
Endometrial component of the menstrual cycle
Proliferative phase
secretory phase
atretic phase
Ovarian cycle
requires LH/FSH input from ant pituitary
LH and FSH promote development of androgen secreting cells surrounding the follicle –> proliferation
high levels of circulating androgens –> ovulation of mature oocyte
following ovulation, androgen profile changes dramatically to inhibit subsequent ovulation
Early ovarian follicular phase
Primary follicles respond to increasing FSH, develops theca/granulosa cells
LH: promotes theca cells to increase androstenedione production
FSH: promotes granulosa cells to increase estradiol production
Estradiol promotes local sensitivity in each developing primary follicle
- granulosa cell proliferation
- estrogen receptor expression, insertion
- FSH receptor expression, insertion
- LH receptor expression, insertion on granulosa cells
Late ovarian follicular phase
first follicle to develop LH receptors on granulosa cells = dominant follicle
Dominant follicle responds to LH with estrogen surge in plasma
Estrogen surge: positive feedback effect on ant pituitary –> increased LH production
LH SPIKE prior to ovulation
Dominant follicle inhibits sister follicle development (paracrine)
Steroid production during ovarian follicular phase
initiated by LH binding to theca cell
FSH binding to granulosa cell: conversion of androgens to estrogen by aromatase
LH receptors on dominant follicle greatly enhance estrogen production
Ovulatory phase
LH surge: due to estrogens from dominant follicle –> critical for ovulation
Requires 2 days of elevated estrogen
LH surge triggers ovulation by:
- neutralized action of oocyte maturation inhibitor
- increased enzyme prostaglandin endoperoxidase synthase
–> PG, thromboxane, leukotriene production to break down ovary wall
Contraction of follicular wall
Ovarian luteal phase
In response to elevated LH, granulosa/theca cells form the corpus luteum
Luteal cells respond to LH by producing estrogen, progesterone
If oocyte is not fertilized, luteal cells degenerate after 12 days
–> decreased progesterone as a result
–> will stimulate ant pituitary to start next cycle
Proliferative phase of endometrium
cells lining uterus divide in response to estradiol from granulosa cells, forming layers of glands and blood vessels
Secretory phase of endometrium
after ovulation, cell division halts
progesterone augments blood supply and initiates secretion of acid mucin
Atretic phase
in absence of fertilized oocyte, progesterone decreases –> loss of uterine lining
produces bleeding for 2-4 days
next cycle begins on day 1 of bleeding and marked by an increase in FSH
Regulation of ovulation during follicular phase
Onset of cycle: loss of estrogen/progesterone from luteal cells –> drive increasing FSH levels
follicular development, increasing estrogen
estrogen levels during follicular phase are LOW and feedback to inhibit GnRH/LH release
inhibin from granulosa cells inhibit release of FSH
Regulation during luteal phase
estrogen drops, progesterone rises
Progesterone inhibits GnRH, FSH, LH
prevents new follicular formation/ovulation
when oocyte not fertilized, corpus luteum atrophies - progesterone levels drop, removes inhibition
cycle begins again with increasing FSH
Early follicular phase overview
low hormone activity
releases negative feedback at hypothalamus and ant pituitary (due to low progesterone)
FSH rises - folliculogenesis, estradiol release at ovary
Mid follicular phase overview
Estradiol levels increase:
- follicles grow
- endometrium proliferates
Late follicular phase overview
Dominant follicle “seleted” - first to develop LH receptor
estradiol surge from dominant follicle in response to LH
Endometrium thickening
cervical mucous changes
dominant follicle suppresses growth of other follicles
Overview of early luteal phase
estrogen surge –> positive feedback on ant pituitary –> LH surge
- first meiotic division
- ovulation
- corpus luteum: produces progesterone, neg feedback on LH, FSH
Overview of mid luteal phase
Progesterone levels rise
organization of endometrium
Late luteal phase overview
w/o fertilization, CL degenerates after 12 days
estradiol/progesterone levels drop
endometrium sloughs - menses
Histology of endometrium during follicular phase
Proliferative phase (growth) endometrial stroma thickens, glands elongate no crowding
Histology of endometrium during luteal phase
Secretory (stabilization)
estrogen/progesterone mediated
endometrial stroma becomes loose and edematous
blood vessels become thickened and twisted
endometrial glands tortuous
>50% ratio glands to stroma