female repro vallano Flashcards
ovarian cycle- series of hormone mediated changes in ovaries leading to monthly production of ovum in women of repro age
- before puberty, ovary has dormant primordial follicles. after puberty, they start to ripen each menstrual cycle. only one follicle becomes a mature Graffian follicle and the others regress. after ovulation and the ovum release, the mature follicle involutes and forms the corpus luteum which sticks around till the end of the cycle.
- in follicular phase: FSH stimulates follicle development. also rising estradiol.
- ovulatory phase: LH surge causes rupture of mature Graffian follicle and oocyte release mid cycle.
- luteal phase: LH converts the ruptured follicle to a corpus luteum. also have high progesterone. some estradiol.
- degeneration of corpus luteum to corpus albicans if fertilization doesnt occur. low estrogen and progesterone.
- the primary follicle secretes estrogens, mostly beta estradiol. through positive feedback of estrogen, estrogen levels get so high that you cause positive feedback and LH surge from the anterior pituitary.
- LH acts on the left over corpus luteum to produce steroid hormone , progesterone, to promote gestation.
primordial follicle increases in size during the ovarian cycle and has the ovum, thecal, and granulosa cells
- granulosa cells are more on the inside layer. they have the aromatase enzyme and the make estrogen.
- thecal cells are more outside, and the feed the granulosa cells the precursors of estrogen. vasculatization of thecal cells is good. recursor is LDL.
- antrum is a fluid cavity w/ increased levels of hormone that sustain the follicle.
endometrial phases
proliferative phase: estradiol dominates. like in the ovarian follicular phase. prolifration of the endometrium promoted. uterus gets primed for progesterone actions by increasing number of receptors for progesterone. this can vary in number of days, usually 14 days in a 28 day cycle and menstrual phase is part of it.
- menstrual phase is part of secretory/proliferative. associated w/ prostaglandin mediated vasoconstriction of spiral arteries and local ischemic injury. regression of the corpus luteum.
- secretory phase is always 14 days. it is progestone dominated and is same time as luteal phase. it is 14 days, from the time you ovulate to corpus luteum degenerates,
- progesterone in the secretory phase promotes accumulation of glycogen, increased glandular secretions, and increased vascularity.
positive and negative feedback
- in late follicular phase, estrogen is dominant. hypothalamus releases gnRH into anterior pituitary, and cells of AP release LH and FSH. LH acts on theca cells to make androgen precursors for the granulosa cell. FSH acts on the granulsa cell which has the aromatase enzyme to make estrogen.
- estrogen feedback on anterior pituitary and on hypothalamus to increase release of GnRH and FSH and LH so you can keep increasing estrogen since we’re in the follicular phase. This is LH and FSH surge.
- in the luteal phase, you have high progesterone and you converted the ruptured follicle to a corpus luteum. GnRH stimulates anterior pituitary to release FSH and LH again, but progestins and inhibins from the granulosa cells cause negative feedback on the pituitary and the hypothalamus to decrease release.
- estradiol, progesterone, and inhibin made by the granulosa cells all have negative feedback actions on the gonadotropin release during luteal phase.
LH secretion is pulsatile, just like GnRH secretion, and it increases in amplitude in follicular phase
- in late follicular phase, the positive feedback of the estrogen causes increase GnRH receptors on anterior pituiary gonadotroph cells which leads to the surge of LH.
- the surge of FSH and LH is necessary for the rupture of the growing follicle.
- gonadotrophs are exposed to same amt of GnRH but they respond more vigorously bc they have more receptors bc of estrogen.
positive and negative feedback
- FSH bings to receptors on granulosa cells and stimulates gene transcription for emzymes like aromatase, activins, and inhibins.
- LH binds receptors on theca cells and stimulates biosynthesis of progestins and androgens. the androgens enter granulosa cells and are converted to estrogen by aromatase.
- granulsa cells respond to FSH but they also have LH receptors.
regulation of gonadotropin secretion
- GnRH binds, activates PLC and Ca release. Formation of DAG and IP3. DAG stimulates PKC, which upregulates gene transripition and production of FSH and LH.
- LH and FSH are alpha beta dimers. They have identical alpha subunits and diff beta subunits.
- gonadotrophs are synthesized, dimerized, and glycosylated in secretory pathway regulated by rythm of GnRH.
- Ca triggers release.
estrogen and progesterone are cholesterol derived
- ovary makes estrogen and progesterone steroid hormones.
- 10-80X more potent is estrogen than its precursors.
- bind albumin and sex hormone binding globulin in serum
- effects on breast, bone, vagina, cervix, fallopian tubes, uterus
- estrogen is inacivated in liver by conjugation w/ glucoronic or sulfuric acid. excreted in urine and bile.
- progesterone is degraded in liver to steroids w/ no progestational effect and urine excreted.
- ovary diff from testes bc high level of aromatase
2 cell, 2 gonadotropin model
- if you have an LH receptor, you can make progesterone.
- theca cells are major ones w/ LH receptor, but granulosa cells have it too. granulosa cells dont have enzymes 17alpha hydroxylase and 17.20 desmoalse to make progesterone into sndrostedione so they use the theca cells to get anrostedione. granulosa cells have aromatase, so they can make estrogen from androstedione. theca cells dont have aromatase, so they make testosterone from androsedione.
- both LH and FSH act on theca ans granulosa cells through a g protein, AC, camp mechanism
- in granulosa cells, the progesterone synthesis through LH receptor only happens in luteal phase.
- in follicular phase, major product of follicle is estradiol
- in luteal phase, major product os progesterone, but estradiiol snthesis still occure.
- activated steroid hormone receptors bind stretches of DNA called SREs, steroid hormone response elements and stimulate gene transcription:
- in follicular phase: estrogen induces endometrial gene products that promote growth and induces progesterone receptors, priming the uterus for progesterone actions in luteal phase.
- n luteal phase, progesterone induces genes that convert uterus to secretory type, promoting glycogen storage and secretion of carb rich mucus)
- estrogen effects in follicular phase: proliferation of uterine endometrial stroma, and development of endometrial glands, prolferation and development of mucosal lining of fallopian tubes, stimulation of bone growth and inhbition of osteclasts, increased fat deposition in subcutaneous tissue.
- progesterone effects in luteal phase: secretory changes in uterine endmetrium, decrease freq and intensity of uterine contractions, increased fallopian tube secretion
- temp drops w/ estrogen high and increases w/ progesterone high
puberty: transistion to cyclic female repro function
thelarche: breast development
adrenarche: increased secretion of adrenal androgens
menarche: menstrual cycle begins
- steroid hormone production on puberty promotes secondary sex characteristcs
- estrogen: inhibits osteoclast activity in bone, so promotes rapid growth anf then uniting of epiphysis w/ shafts of long bones to stop growth
- estrogen promotes deposition of fat, development of stromal tissueand ductile growth of breasts
- progesterone promotes development of lobules and alveoli in breasts
-before puberty, release of gonadotropins is inhibited by low amts of sex steroids/estrgen. this means negative feedback sensitivity is high. in children, a low level of steroid estrogen blocks gonadotropin. in adults, a much much higher level is needed to block gonadotropins. in infancy, you are very sensitive to gonadotropin release to negative feedback by sex steroids and in adults youre less senstive.
-the axis becomes functional in puberty. hypothalamus in child can be triggered to release GnRH. pituitary responds and releases FSH and LH. the gonads respond normally to FSH and LH. but, activating the hypothalamus is immature until puberty!
-at puberty, pulsatile secretion of GnRH is seen first at night then at day and night. steroid hormone production causes secondary sex characteristics and normal ovarian function.
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menopause
cessation of cyclic repro function and menstruation
- avg age is 51-52 years but can occur earlier
- no remaining ovarian follicles
- level of circulating sex steroids decreases, ut you have some peripheral conversion, at the adrenal
- level of circulating gonadotropin increases
- bunch of physical and mental changes
- vasomotor instability hot flashes, night sweats, mood changes, short term memory loss, sleep issues, headaches, libido loss, atrophy of vagina epithelium, vaginal pH changes, less vaginal secretions, less blood to vagina dna uterus, pelvic relaxation, loss of tona of vagina, cardiovasclar diases and osteporosis. estrogen and progesterone are protective against cardiovascular diases.
at menopause, no remaining ovarian follicles to respond to FSH and LH leading to decline of estrogen production
- you have 6-7 million germ cells in ovaries in 20 week fetus
- declies to 1-2 million at birht
- at puberty, 400,000 germ cells. each month, a population responds to FSH and one dominates
- 400 oocytes are ovulated in life
- menopausal wonen have no follicles or few follciels to mature and produce estrogens and progestins
- there is ongoing atresia of cells througout reproductive life, accounting for most of follicle loss
reduced estrogen leads to increased gonadotropin production on menopausal women
at menopuse, you have abrupt increase in gonadotropic hormones
- FSH increases 17X but clearance rate is stable
- LH increases 3X but clearance rate is stable
- these are diagnostic of menopase.
- circulating gonadotropin increase dramatically bc of loss of negative feedback on pituitary and hypothalamus by estrogen and prgesterone.
- increased LH anf FSH is due to increased production, not decreased clerance.
