206. Endocrine Control, Female Repro I Flashcards
What are the components of a follicle (6)?
What are the 5 phases of follicle development?
- oocyte
- GCs (surround egg and follicle), cumulus oophorus “cloud of egg”
- theca cells
- basal lamina: separates theca and GCs, follicle is AVASCULAR
- Zona pellucida: secreted by oocyte, glycoprotein egg shell
- antrum: filled with follicular fluid, micro-enviro for follicle to have higher hormone conc
- Primordial: primary oocyte and flattened GCs
- Primary: larger oocyte, cuboidal GCs, gap junctions form (so cells respond synchronously to hormones)
- Preantral: GC proliferate, zona pellucida present, theca cells appear
- Antral: follicular fluid grows, forming antrum
- Pre-ovulatory: oocyte, GC differentiate to cumulus oophorus
Ovarian Steroid Hormones
- Which cells make androgens? What stimulates androgen production?
- which cells make E? What stimulates E production?
- What enzyme helps gonads make T/E? Where else is it present?
- What situations increase or decrease SHBG?
Theca Cells: triggered by LH to make androgens - diffuse to GCs
GCs: triggered by FSH to make more aromatase - convert androgens from theca cells to E (GCs develop LH receptors as they mature to make P)
Gonads: express 17-beta dehydrogenase = increase T/E production (enzyme found all over body tissue); aromatase converts T to E (in GCs-ovary, brain, adipose)
SHBG: higher levels in hyperthyroidism, pregnancy, E tx (less free hormone b/c more bound); lower levels with glucocorticoids, androgens, P, GH/IGF1, Insulin (more hormone free)
How does GnRH stim FSH and LH?
Tx for GnRH agonism vs. antagonism
LH: high frequency GnRH pulses
FSH: low frequency GnRH pulses
Continuous GnRH pulses: DESENSITIZATION (uncoupling of receptor and signaling pathway, receptor internalization)
GnRH agonism/antagonism: precocious puberty, endometriosis, fibroids, prostate cancer (suppress T/E)
complications: osteoporosis, hot flashes, vaginal dryness (low E)
What are the functions of FSH (4) and LH (3)? How do GnRH pulses vary throughout menstrual phases?
How do E levels affect feedback?
FSH: promote GC proliferation, induce more FSH receptors, induce aromatase (increase E), induce LH receptors
LH: androgen production in theca cells, induce ovulation, support corpus luteum
Follicular phase: low amp, low frequency = HIGH FSH
Ovulation: high freq = LH SURGE
Luteal phase: low freq, high amp to support corpus luteum (LH)
Negative feedback: high E suppresses GnRH (less pit secretions)
Positive feedback: when E sustained at high concentrations = LH surge = trigger ovulation
Ovarian Peptide Hormones
- where are they synthesized and secreted?
- Inhibin: when are they stimulated, what inhibits them
- Activin: where are they, what do they do
- Follistatin: what is it, how is it regulated
Synthesized in GCs, secreted into follicular fluid (endocrine, paracrine signals)
Inhibin:
- fx: inhibits FSH = less synthesis/secretion of FSH, less GnRH receptors, more FSH degradation
- stimulated by FSH (negative feedback)
- Inhibin B: high in follicular phase
- Inhibin A: stim by LH, high in luteal phase
Activin
- expressed in pit or GC (secreted to follicle fluid)
- augments FSH: increases GnRH receptors in pit, increases FSH receptors in ovary
- paracrine effects
Follistatin
- FSH suppressing protein: binds activin to neutralize activity
- expressed in pit, GC
- regulation: activin stimulates follistatin, inhibin inhibits follistatin
How does dominant follicle selection occur during follicular development?
Pre-antral follicles:
GCs express FSH-R; FSH rescues follicle from atresia (induces more FSH-R, promotes GC proliferation and follicle growth, increases aromatase = more E)
Pre-Antral -> Antral Follicle
FSH continues to promote GC proliferation = more follicle size, more inhibin, more aromatase (more E)
FSH begins to induce LH-Rs on GCs
Higher E causes less FSH due to negative fb to pit
Dominant Follicle Selection
less FSH from ant pit = atresia (not enough aromatase, androgen buildup, LH-Rs inhibited)
Dominant follicle: selected by having most FSH-Rs, can make aromatase (high E), has LH receptors: continues to grow = causes P production (needed preovulation
How does ovulation occur?
High E from dominant follicle (and some increased P augments) = LH surge through pos fb = increased pit sensitivity to GnRH
LH SURGE: meiosis of egg resumes, cumulus expands, increased PG synthesis (frees proteolytic enzymes = divide GC connections, contract smooth muscle around follicle), increase GC P synthesis
Progesterone: relaxes follicle wall (for increased follicular fluid), enhances proteolytic enzymes, small FSH surge (increase LH-R’s for luteal phase on GCs)
Release of oocyte and cumulus from ovary
How does the corpus luteum form and regress?
- Reorganization of dominant follicle: GC/theca cells become luteal cells - proliferate, enlarge, accumulate lipid droplets, increase smooth ER/mito (more steroid producing machinery); increased blood supply causes dissolved basal lamina (blood vessels enter), angiogenesis, cholesterol delivery for steroid synthesis
- CL produces P: prepare/support endometrium for pregnancy, peaks 7 days after ovulation (uterine lining, differentiation, secretion)
- CL requires continuous LH secretion by GnRH stim (inhibited by rising P and E from CL)
- Regression occurs ~14days after LH surge, less LH due to more E/P, declining E/P = shedding of endometrium
- Pregnancy RESCUES CL: hCG binds FSH-R and LH-R on CL, CL P/E production continue to W10 and critical for early pregnancy development
Placenta: begins steroidogenesis at W7, major fetal steroid source at W10
What part of the menstrual cycle is fixed among women? Which is variable?
When is Day 1 of the menstrual cycle?
Luteal Phase FIXED at 14 days
Menstrual/Follicular Phase vary depending on cycle length (ovulation not always Day 14)
Day 1 of cycle: 1st day of menstrual bleeding
