Unit 7 - Female Reproductive Endocrinology Flashcards
phases of the ovarian cycle
series of hormone-mediated changes in ovaries culminating in monthly production of viable ovum in women of reproductive age
- follicular - FSH stimulates development of follicles; rising estradiol
- ovulatory - LH surge causes rupture of mature Graafian follicle and oocyte discharge (mid-cycle)
- luteal - LH converts ruptured vollicle into corpus luteum; high progesterone plus some estradiol
2 functions of ovaries
- produce/release ova
- produce hormones
when does degeneration of corpus luteum into corpus albicans proceed?
if fertilization doesn’t occur (low estrogen and progesterone)
what is the most important estrogen?
beta-estradiol
what happens to the ovary as one progresses from pre-puberty to after puberty?
before: ovary has many primordial follicles that stay dormant
after: several follicles ripen each menstrual cycle, but only 1 matures (the others regress)
- after ovulation and ovum release, the mature follicle involutes to corpus luteum, which stays to the end of the cycle
maturation of ovarian follicle
primordial follicle - 30-60 um in diameter, and production from primary oocytes is complete by 6 mo of age
primary follicles - develop during monthly ovarian cycle to secondary –> early tertiary follicle
graafian follicle - attains diameter of 20-33 mm
what is the antrum of a follicle?
in early tertiary and graafian follicles
- fluid filled cavity that sustains the follicle
- has very high [hormone]
where are thecal cells on follicles?
the outside; good vascularization
how does the ovarian cycle coincide with the endometrial cycle?
follicular phase = proliferative phase (varies, ~11 days)
luteal phase = secretory phase (FIXED AT 14 DAYS)
corpus luteum regression = menstrual phase (usually divided between follicular and luteal phases)
endometrial cycle phases
- proliferative - thickness of endometrium increases from 1-2 mm to 8-10 mm
- dominated by estrogens and variable in length - secretory - dominated by progesterone with fixed length of 14 days following ovulation
- progesterone promotes accumulation of glycogen, increased glandular secretions, and increased vascularity - menstrual - prostaglandin-mediated vasoconstriction of spinal arteries and local ischemic injury/inflammation
- regression of corpus luteum
how do coordinated hormonal secretions prepare uterus?
- estradiol (follicular phase) promotes proliferation of endometrium and “primes” uterus for progesterone actions by increasing progesterone receptors
- progesterone (luteal phase) converts proliferative uterus to secretory uterus (enhance differentiation of epithelial and stromal cells, promoting glycogen storage and secretion of CHO-rich mucus)
late follicular and ovulatory phases feedback
GnRH (from hypothalamus) –> pituitary –> LH/FSH
- LH –> thecal cells (make androgens) and granulosa cells (make estrogens and activins)
- FSH, androgens –> granulosa cells only
- estrogens –> pituitary and hypothalamus via positive feedback
- activins –> acts on AP only
luteal phase feedback
same as usual, but this time theca cells make progestins and androgens, and granulosa cells (corpus luteum) make progestins, estrogens, and inhibins
- progestins and estrogens feedback negatively on pituitary and hypothalamus
- inhibin works only on FSH on AP
how are GnRH and LH “pulsatile”?
pulsatile release of GnRH in both early and late follicular phases causes LH rises (“surge” in late)
-high circulating estrogens in LFP “sensitize” AP gonadotrophs to GnRH stimulation to cause the “surge” in LH (and less importantly FSH) release necessary for rupture of growing follicle and ovulation
what happens to androgens from theca cells that are transferred to granulosa cells?
androgens are converted to estrogens in granulosa cells
regulation of gonadotropin secretion
- binding of GnRH to GPCR activates PLC path to release Ca++
- activated PLC also forms DAG to stimulate PKC
- PKC phosphorylates targets that indirectly stimulate gene transcritpion
- stimulated by late follicular phase estrogen and ovarian activin
- inhibited by luteal phase estrogen/progesterone and ovarian inhibin - LH and FSH are alpha-beta dimers with identical alpha subunits (beta determines specificity)
- LH/FSH are made, dimerized, and glycosylated in secretory pathway, regulated by GnRH rhythm
- Ca++ released from internal stores activates Ca++ channels for sustained Ca++ increase
- increasing Ca++ triggers exocytosis and release of gonadotropin
what do steroid hormones bind to in serum?
loosely to albumin and sex hormone-binding globulins (SHBGs)
how are estrogen and progesterone destroyed?
E: inactivated in liver thru conjunction with glucuronic or sulfuric acids, and excreted in urine (less so in bile)
P: rapidly degraded in liver to steroids w/ no effect, and excreted in urine
how do theca and granulosa cells work together to make steroids?
granulosa cells make cholesterol –> progesterone, but lack 17-alpha-hydroxylase and 17,20 desmolase, so progesterone is transferred to theca cells
theca cells make progesterone –> androstenedione (some goes to granulosa cell, some stays)
in granulosa cell, makes testosterone –> estradiol
in theca cell, make testosterone (no aromatase)
what is the main source for cholesterol to make steroid hormones?
LDL (receptors in both theca and granulosa cells)
estrogen effects
- proliferation of uterine endometrial stroma and development of endometrial glands
- proliferation and development of mucosal lining of fallopian tubes
- stimulation of bone growth by inhibition of osteoclastic activity, followed by uniting of epiphysis with shafts of long bones to stop growth
- increased fat deposition in subcutaneous tissues
- development of stromal tissue and ductile growth in breasts
progesterone effects
- secretory changes in uterine endometrium (major)
- decreased frequency and intensity of uterine contractions
- increased fallopian tube secretions
- promotes development of lobules and alveoli in breasts
stages of puberty
transition to cyclic female reproductive function
- thelarche - breast development
- adrenarche - increased secretion of adrenal androgens cause pubic hair
- menarche - menstrual cycles start
why does the hypothalamus not cause menses if not puberty?
in a child, even low level of steroids blocks release of gonadotropin; higher levels are needed to inhibit as grow older
-pulsatile secretion of GNRH is observed first at night, then during day as well
what is menopause?
cyclic reproductive function and menstruation cease
- average 51-52 years, but occurs earlier
- no remaining ovarian follicles
- levels of circulating sex steroids decrease (some peripheral conversion - adrenal)
- levels of circulating gonadotrophins rise
- physical and mental changes
menopausal syndromes
- vasomotor instability
- hot flashes
- night sweats
- mood changes
- short-term memory loss
- sleep disturbances
- headaches
- loss of libido
menopausal physical changes
- atrophy of vaginal epithelium
- changes in vaginal pH
- decrease in vaginal secretions
- decrease in circulation to vagina and uterus
- pelvic relaxation
- loss of vaginal tone
- CVD, osteoporosis, and maybe Alzheimer’s
why does steroid hormone production decline dramatically in menopause? how are levels of FSH and LH?
almost no remaining ovarian follicles to respond to FSH and LH
- FSH and LH are sustained high (10-20x) b/c losing inhibition
- -increased production, not change in clearance
how does the number of germ cells in women change with age?
peak of 6-7 million germ cells in 20 week fetus alone
- at birth, decrease to 1-2 million
- by puberty, ~400,000, and each month a population of cells respond to FSH with only 1 dominating (only 400 are ovulated, most are atresia’d)
- menopausal women have few/no remaining follicles to mature and make estrogens/progestins
what is estrone?
15-25% as potent as estradiol
- made by muscle and adipose tissue, and made from androstenedione in adrenal gland and ovary
- provides postmenopausal source of esrogen
