Female Reproductive Flashcards
In the female, what cell type is homologous to: Leydig cells? Sertoli cells?
Leydig cells ~ Theca cells (LH → androgen producing)
Sertoli cells ~ granulosa cells ( both stimulated by FSH (earlier follicular phase))
What is the role of ovarian granulosa cells in a 2-9mm diameter non-dominant, antral follicle?
- under the influence of FSH → produce estradiol from androstenedione from theca cells
- FSH stimulates inhibin B synthesis and release → inhibits granulosa cell proliferation
What is the role of ovarian granulosa cells in a 15-20 mm diameter dominant, antral follicle?
- under the influence of FSH and LH → produce estradiol from androstenedione and testosterone from theca cells and directly from cholesterol
- LH stimulates inhibin A and FSH stimulates inhibin B synthesis and release → inhibits granulosa cell proliferation
What is the role of theca cells in terms of steroid production in ovarian antral follicles females in the follicular phase in both non-dominant and dominant follicles?
Under the influence of LH, theca cells produce progesterone, androstenedione (main output) and some testosterone
What is the role of ovarian luteal cells in a corpus luteum (in terms of steroid hormone and inhibin production, and gonadotropin receptor expression) in the early luteal phase?
in response to LH surge → progesterone synthesis, LH still stimulates inhibin A synthesis
What is the role of ovarian luteal cells in a corpus luteum in terms of steroid hormone in the mid-to-late luteal phase
LH stimulates progesterone and estrodiol production, LH still stimulates inhibin A synthesis
granulosa cells
- produce estradiol (from androgen precursor)
- stimulated by FSH (in early follicular phase) and by LH and FSH (mid-late follicular phase)
theca cells
produce progesterone, androstenedione, and some testosterone
- provides androgen precursors to ovarian follicle granulosa cells
- stimulated by LH
luteal cells
- from granulosa and theca cells
- produce progesterone, estradiol, inhibin A
LH receptors
located on theca cells, located on granulosa cells in mid-late follicular phase and thereafter
FSH receptors
located on granulosa cells in follicular phase
List reproductive actions of estrogen and progesterone in females
- Development of genitalia & breast, female fat distribution
- Growth of follicle, endometrial proliferation, increase myometrial excitability
- Upregulation of estrogen, LH, & progesterone receptors; feedback inhibition of FSH & LH then LH surge; stimulation of prolactin secretion
AMH regulation of ovarian follicle growth
- produced by primary, secondary, and non-dominant follicles
- diminishes onset of follicle growth at primordial stage
- diminishes FSH action on non-dominant follicles
- *circulating AMH levels good biomarker for number of follicles growing
follicular phase
- days 1-14
- fall in progesterone, estradiol, inhibin A from corpus luteum –> increase in FSH, LH
- onset of menstrual bleed
- FSH –> 6-20 follicles to grow
- follicles secrete estradiol and inhibin B (estradiol stimulates proliferation of endometrium)
- inhibin B inhibits FSH (neg feedback) so FSH levels fall
- BUT largest follicle (dominant) develops LH receptors on mural granulosa cells, so LH supports survival
- dominant follicle produces estradiol (positive feedback)
Ovulation
- dominant follicle releasing estradiol –> gene transcription in hypo
- -> GnRH surge
- ->causes LH surge
- -> ovulation (day 14) from enzymes dissolving matrix around oocyte
- stimulates oocyte meiosis from Prophase I to Metaphase II
- *LH surge converts follicle cells into luteal cells secreting progesterone
Luteal Phase
- days 14-28
- LH receptors on luteal cells, so supports progesterone and estradiol secretion
- corpus luteum secretes progesterone
- -> matures endometrium (secretory phase), negative feedback on GnRH/LH & FSH
- *Inhibin A contributes negative feedback on FSH
- early decrease in estradiol, then rise
- -days 26-28: luteal cells unresponsive to LH, endometrium will shed without progesterone support
Polycystic ovarian syndrome
Diagnosed from at least 2 criteria:
- clinical (hirsutism, Ferriman-Gallwey >8) or biochemical (high testosterone) hyperandrogenism
- intermittent (3 months w/o pregnancy) menstrual cycles
- polycystic ovaries
- *need to eliminate mimics: congenital adrenal hyperplasia, Cushing’s syndrome, hyperprolactemia, hypothyroidism, androgen-secreting tumors, and hypothalamic amenorrhea
commonly accompanied with metabolic syndrome, type 2 diabetes, obesity, and sleep apnea
- theca cell proliferation, excess androgen secretion
- increased AMH from having more non-dominant follicles
- increased circulating testosterone and androstenedione levels
- infrequent/no ovulation
- increased LH, so decreased negative feedback of estradiol/progesterone
Oral contraceptives
- combined: estrogen and progestins
- progestin only pills
- *use negative feedback to prevent ovulation (like luteal phase)
Premature ovarian failure
- loss of sufficient numbers of follicles to maintain negative feedback regulation before age 40
- low estradiol (and other ovarian hormones), leads to high FSH/LH, absent menstrual cycles
- replacement hormone therapy
Functional hypothalamic amenorrhea
- low LH and FSH (and GnRH?) leading to low ovarian hormones and absent menstrual cycles
- treat with GnRH pump or recombinant gonadotropin treatment
- also treat with cognitive behavioral therapy
- *can occur due to weight loss or excessive exercise
Primary Amenorrhea
- after girl is 16 years and has undergone other normal changes with puberty (just not menarche)
- LH and FSH low/high with low ovarian hormones
- causes: many, including Kallmann and Turner (XO) syndromes
Secondary Amenorrhea
- when previously menstruating woman stops having periods
- most likely from pregnancy
- also could be from oral contraceptives, stress, eating disorders, PCOS, excessive exercise, & more.
Menopause stages
1) initial signs (ages 38-45 years)
- monotropic rise in FSH in early-mid-follicular phase
- no elevation in LH, but falling AMH levels (from decreased inhibin B rise from less growing follicles)
- estradiol-responsive follicles have increased estradiol secretion due to elevated FSH
2) Menopause transition
- elevated FSH (possibly LH)
- lower estradiol in follicular phase
- intermittent cycles
3) Menopause
- elevated FSH (usually LH too)
- no cycles
- low estradiol, androgens, AMH
Abortion pill
- post-ovulatory contraception
- progesterone receptor antagonist plus a prostaglandin E1 analogue for muscle contraction
- induces miscarriage before 8 weeks (afterwards, placenta takes over)
