SM_206b: Endocrine Control Female Repro I Flashcards
Describe reproductive functions
Reproductive functions
- Produce gametes
- Male: deliver gametes to site of fertilization
- Female: provide environment for fertilization and fetal growth and nutrients for newborn
Describe female reproductive anatomy
Female reproductive anatomy
- Ovary: gametes, hormones
- Fallopian tube: fertilization, early embryo development
- Uterus: fetal growth
Describe the menstrual cycle
Menstrual cycle
- Basis for female human reproduction
- Coordinated events: ovary (ovulation), uterus (preparation of lining)
- Monthly (approximately)
- Day 1 is first day of bleeding
Menstrual cycle involves the ____
Menstrual cycle involves the hypothalamic-pituitary-ovarian axis
- Hypothalamus secretes GnRH
- Anterior pituitary secretes LH and FSH
- Ovary secretes estrogen and progesterone
- Acts on uterus
GnRH is produced in ____, secreted in ____, and regulated by ____
GnRH is produced in specific hypothalamic neurons, secreted in portal circulation, and regulated by higher brain centers
- Does not circulate in body
Gonadotropins (FSH, LH) are produced by ____ in ____ and stimulated by ____
Gonadotropins (FSH, LH) are produced by gonadotrophes in anterior pituitary and stimulated by GnRH
- Glycoproteins, common alpha subunit (also in hCG and TSH), specific beta subunit
FSH promotes ___
FSH promotes follicle development in ovary
LH supports ____
LH supports corpus luteum
Oocytes develop in ___
Oocytes develop in follicles
- Oocyte
- Granulosa cell: cumuls oophorous
- Theca
- Basal lamina: separates theca and granulosa cell, follicle is avascular
- Zone pellucida: secreted by oocyte, glycoprotein egg shell ,a ntrum filled with follicular fluid and micro-environment
Follicular development involves ____, ____, ____, ____, and ____stages
Follicular development involves primordial, primary, preantral, antral, and preovulatory stages
- Primordial (50 uM): primary oocyte (20 uM), flattened granulosa cell
- Primary: larger oocyte (80 uM), cuboidal granulosa cell, gap junctions form
- Preantral (200 uM): granulosa cell proliferated, zone pellucida present, theca cells appear
- Antral (500 uM): follicular fluid -> antrum
- Pre-ovulatory (2o mm): oocyte (150 uM), granulosa cell differentiates into cumulus
Describe ovarian cycle
Ovarian cycle
- Many follicles are recruited (make estrogen)
- 1 dominant follicle selected (others die)
- Dominant follicle releases egg (ovulation)
- Corpus luteum develops (make progesterone and estrogen)
Corpus luteum is ____
Corpus luteum is reorganization of the ovulated follicle
- Granulosa and theca cells -> luteal cells: produce progesterone and estrogen
- Basal lamina dissolves: cell types intermingle, blood vessels enter (deliver cholesterol for hormone synthesis)
Describe ovarian steroid production during the menstrual cycle
Ovarian steroid production during the menstrual cycle
- Follicular phase: estrogen increases
- Luteal phase: estrogen and progesterone produced
- If no pregnancy: corpus luteum dies -> hormone levels fall
- Estrogen -> proliferation of the endometrium (uterine lining)
- Progesterone -> differentiation: glands develop, fill with glycogen (prepare for pregnancy)
- If not pregnant -> hormones decline: endometrium sheds
Menstrual cycle is divided into phases and consists of ____ cycle and ____ cycle
Menstrual cycle is divided into phases and consists of ovarian cycle and uterine cycle
Ovarian cycle consists of ____, ____, and ____
Ovarian cycle consists of
- Follicular (10-22 days): development of egg
- Ovulatory (36 hours): release of egg
- Luteal (14 days): corpus luteum
Uterine cycle consists of ____, ____, and ____
Uterine cycle consists of proliferative, secretory, and menstruation
- Proliferative: growth of endometrium
- Secretory (14 days): differentiate endometrium
Menstruation (4-5 days): shed endometrium
Ovarian steroid hormones are ____, ____, ____, and ____
Ovarian steroid hormones are cholesterol, progesterone, androgen, and estrogen
- Cholesterol (27C)
- Progesterone (21C)
- Androgen (19C): testosterone, DHEA, androstenedione
- Estrogen (18C): estradiol (E2), estrone (E1), estriol (E3)
- Specific enzymes required
Aromatase ____
Aromatase converts androgens to estrogens
Describe ovarian hormone production
Ovarian hormone production
- Theca cells make androgens
- Granulosa cell makes aromatase to convert androgens to estrogen
- Antrum increases local estrogen levels
Describe 2 cell, 2 gonadotropin theory of estrogen production
2 cell, 2 gonadotropin theory of estrogen production
- Theca cells have LH receptors: produce androgens
- Androgens diffuse into granulosa cells
- Granulosa cells have FSH receptors: produce estrogens
- FSH increases aromatase
- Aromatase converts androgens to estrogens
- BUT granulosa cells get LH receptor later
____ is gonadal enzyme involved in estrogen synthesis
17 B-HSD is gonadal enzyme involved in estrogen synthesis
____ and ____ are adrenal enzymes involved in estrogen synthesis
21 hydroxylase and 11 B-HSD are adrenal enzymes involved in estrogen synthesis
Extra-glandular sex steroid production involves ____ and ____
Extra-glandular sex steroid production involves 17 B-HSD and aromatase
- 17 B-HSD: gonads, other tissues
- Aromatase: granulosa cells in ovary, brain, adipose (source of most estradiol in men)
Dihydrotestosterone is a ____ made at ____
Dihydrotestosterone is a potent androgen made at the site of action
- Little circulates
- Non-aromatizable
5 alpha reductase converts ____ to ____
5 alpha reductase converts testosterone to 5 alpha dihydrotestosterone
- In peripheral tissues
- Type 1: adults
- Type 2: fetal life
Estrogen and testosterone are transported through blood primarily ____
Estrogen and testosterone are transported through blood primarily bound to SHBG
- Bound hormones are not biologically active
DHEA, androstenedione, and dihydrotestosterone are transported through blood primarily ____
DHEA, androstenedione, and dihydrotestosterone are transported through blood primarily bound to albumin
- Bound hormones are not biologically active
Describe sex hormone binding globulin
Sex hormone binding globulin
- Glycoprotein
- Increases with hyperparathyroidism, pregnancy, estrogen treatment
- Decreases with glucocorticoids, androgens, progesterone, GH / IGF-1, insulin
GnRH is a ____
GnRH is a decapeptide
- Rapidly degraded by peptidases
- Stimulates FSH and LSH
- Precursor is prepro-GnRH
- GnRH neurons migrate
GnRH secretion rises during ___
GnRH secretion rises during puberty
Describe GnRH secretion during early puberty
GnRH secretion during early puberty
- During sleep: increased GnRH (increased LH and FSH)
- Increased estrogen: thelarche, female fat, growth, vaginal changes
Describe GnRH secretion during later puberty
GnRH secretion during later puberty
- Pulsatile secretion over 24 hours
- Mid-puberty: menarche (first menstrual period): estrogen stimulates uterine lining proliferation, timing 12.8 years (median)
- Late puberty: ovulation (release of egg): positive feedback of estrogen develops, mature pattern of GnRH secretion during cycle, usually 6-9 months after menarche
Describe GnRH regulation of LH and FSH secretion
GnRH regulation of LH and FSH secretion
- Different pulses: amplitude, frequency
- High frequency: favors LH-beta
- Low frequency: favors FSH-beta
- Continuous pulses: desensitization, decreases FSH and LH
Gonadotrope responsiveness requires ____
Gonadotrope responsiveness requires pulsatile GnRH
Continuous GnRH leads to ____
Continuous GnRH leads to desensitization
- Decreased response with continuous stimulation: uncoupling of receptor and signaling pathway, internalization of receptors
GnRH agonist treatment causes ____
GnRH agonist treatment causes rise in LH but then a fall
- GnRH agonist treatment is used for precocious puberty, endometriosis, fibroids, and prostate cancer
- Complications: osteoporosis, hot flashes, vaginal dryness
Gonadotropin regulation depends on ____
Gonadotropin regulation depends on appropriate patterns of GnRH pulses
- Synthesis: glycosylation, assembly, folding
- Release
Describe gonadotropins during menstrual cycle
Gonadotropins during menstrual cycle
- FSH: promote granulosa cell proliferation, induce FSH receptors, induce aromatase -> estrogen, induce LH receptors
- LH: androgen production, ovulation, supports corpus luteum
GnRH pulses ____ during the menstrual cycle
GnRH pulses vary during the menstrual cycle
Describe negative feedback in hypothalamus-pituitary-ovarian axis
Negative feedback in hypothalamus-pituitary-ovarian axis
- Estrogen mostly but also progesterone
- Decrease GnRH
- Decrease pituitary response
- Decreased beta subunits and decreased GnRH receptors
Describe positive feedback in hypothalamic-pituitary-ovarian axis
Positive feedback in hypothalamic-pituitary-ovarian axis
- Estrogen: sustained high concentrations -> LH surge -> trigger ovulation
- Progesterone rises pre-ovulation -> increased pituitary response -> increased FSH and LH
Ovarian peptide hormones are synthesized in ____ and secreted into ____ for ____ and ____ signaling
Ovarian peptide hormones are synthesized in granulosa cell and secreted into follicular fluid for endocrine and paracrine signaling
- Inhibin
- Activin
- Follistatin
Inhibin ____
Inhibin inhibits FSH
Activin ____ and ____
Activin stimulates FSH release and augments FSH action in ovary
Follistatin ____
Follistatin binds to activin to suppress activity
Describe inhibin
Inhibin
- Inhibits FSH: blocks synthesis and secretion, reduces GnRH receptors, promotes intracellular degradation of FSH
- Reciprocal relationship: FSH stimulates inhibin, and inhibin inhibits FSH
- Inhibin B: increases in follicular phase
- Inhibin A: stimulated by LH and increases in luteal phase
Activin is expressed in ____ and ____ and functions to ____
Activin is expressed in pituitary and granulosa cell (secrete into follicular fluid) and augments FSH
- Increased GnRH receptors in pituitary, increased FSH receptors in ovary
- Paracrine effects
Follistatin ____ by ____
Follistatin suppresses FSH by binding to and neutralizing activin
- Tissue expression: pituitary, granulosa cell
- Regulation: activin stimulates, inhibin inhibits
____ follicle is selected for ovulation
One follicle is selected for ovulation
- Most die by atresia: degenerative process via programmed cell death (apoptosis) in granulosa cell
Describe transition from primordial to preantral follicle
Primordial to preantral follicle
- Hormone independent: granulosa cell have no FSH receptors
- Continues throughout life
- Most preantral follicles undergo atresia
- Preantral follicles: granulosa cell expresses FSH receptors
Describe preantral follicle
Preantral follicle
- FSH rescues cohort: induces FSH receptors -> greater FSH response, promotes granulosa cell proliferation -> follicle growth, increased aromatase -> increased estrogen
- FSH plus estrogen is synergistic
Describe transition from preantral to antral follicle
Preantral to antral follicle
- Requires FSH: promote granulosa cell proliferation, induce FSH receptors on granulosa cell, increased aromatase so increased estrogen, idnuce LH receptor on granulosa cell
- Follicle recruitment: continued growth of antral follicles in response to FSH, rescued from atresia by FSH
- Estrogen -> decreased FSH through negative feedback
Describe dominant follicle selection
Dominant follicle selection
- Day 5-7: decreased FSH
- Most follicles undergo atresia b/c not enough aromatase and androgens build up
- Dominant follicle has most FSH receptors, can make aromatase, and has LH receptors
Describe pre-ovulatory follicle
Pre-ovulatory follicle
- 20 mm in size
- Large antrum: filled with follicular fluid, microenvironment
- Granulosa cells differentiate to cumulus cells
Describe LH surge
LH surge
- Increased estrogen -> dramatic increase in LH through positive feedback, pattern of estrogen rise is critical
- Increase pituitary sensitivity to GnRH, increase GnRH receptors
- Small increase in progesterone augments LH surge
Describe ovulation
Ovulation
- LH surge: meiosis resume, cumuls expands, increased prostaglandin synthesis, increased granulosa cell progesterone synthesis
- Progesteorne: relaxes follicle wall, enhances proteolytic enzymes, FSH surge (increased LH receptors)
Ovulation is ____
Ovulation is release of oocyte and cumulus from the ovary
____ is the yellow body
Corpus luteum is the yellow body
Corpus luteum formation involves ___
Corpus luteum formation involves reorganization of the dominant follicle
- Granulosa and theca cells -> luteal cells
- Increased blood supply
Corpus luteum produces ____ which prepares and supports the ____
Corpus luteum produces progesterone which prepares and supports the endometrium
- Progesterone peaks 7 days after ovulation
Corpus luteum requires ____
Corpus luteum requires continued LH secretion
- Stimulated by GnRH
- Inhibited by increased progesterone and estrogen
Corpus luteum occurs ____ as ____
Corpus luteum occurs 14 ± 2 days after LH surge as estrogen and progesterone levels decline
- Endometrium sheds (menstrual cycle)
- Pregnancy rescues corpus luteum
____ phase is fixed at 14 days, while ____ and ____ phases vary
Luteal phase is fixed at 14 days, while menstraul and follicular phases vary
- Day of ovulation depends on cycle length
____ rescues the corpus luteum
hCG rescues the corpus luteum
- hCG supports corpus luteum
- Corpus luteum steroids continues until 10 weeks, critical for early pregnancy, progesterone peaks 8 days after LH surge if not pregnant
- Placenta: steroidogenesis starts at 7 weeks gestation, hCG is major steroid source is at 10 weeks gestation
Describe female reproduction
Female reproduction
- Menstrual cycle: ovary produces gametes, uterus prepares lining for embyro implantation
- Pregnancy: tube provides environment for fertilization, uterus provides environment for fetal growth
- Lactation provides nutrients for newborn
Menstrual bleeding is in response to ____ and occurs ____
Menstrual bleeding is in response to ovulation and occurs 14 days later
Birth control pills lead to ___ bleeding
Birth control pills lead to hormone withdrawal bleeding
Birth control pills contain ____ and ____ to exert ____to ____
Birth control pills contain ethinyl estradiol (estrogen) and progestins to exert negative feedback to decrease GnRH
- Decreases LH and FSH
Fertility drugs contain ____ to ____
Fertility drugs contain FSH to rescue follicles from atresia
- Normally FSH decreases at day 5-7 and most follicles undergo atresia
