MCDB 240: Ovary III Flashcards
define ovulation
preparation to switch to nurturing of embryo - luteal or progestric stage
describe the results of the LH surge
1) rupture of follicle w/ release of egg
2) cumulus expansion
3) egg maturation
LH also important for lutenization, or formation of corpus luteum
define luteinization
follicle physicall and structurally reorganized
-process of differentiation by which theca and granulosa cells become luteal cells. Results in formation of corpus luteum
define the cell types of the corpus luteum
1) steroidogenic cells (30%, primary)
a) theca lutein cells (small, but very steroidogenically active)
b) granulosa lutein (large, also active)
2) nonstreodogenic
a) endothelial
b) immune cells
c) fibroblasts
define angiogenesis
de novo development of blood cells
define the difference between follicle and the corpus
follicle before had basement membrane to separate theca from granulosa
define luteal angiogenesis
rare process in adult life that is physiologic (in corpus and also in different process in endometrium)
- corpus becomes vascularized
- LH stimulates vascular endothelial growth factor (VEGF) mRNA or protein in luteal cells
- breakdown of basement b/t theca and granulosa
- vascularization of granulosa cells
define the timeline of corpus development
Day 0 - LH surge effects -> ovulation, corpus becomes formed, progesterone produced even before egg is released
Day 1 0 granulosa cells proliferate (differrentiate before, goes back to proliferative state later)
Day 2 - capillary invasion of granulosa layer
Day 7 - max capillary enargement and max production of progesterone
-capillyar brings progesterone/precurors to corpus
-by midluteal stage, max production of progesterone; continues later at lower levels
-takes in cholesterol and exports progesterone
describe the homerrohagic corpus luteum
cyst forms, corpus fxn compromised to generate progesterone, ruptures in abdomen
describe the luteal hormones
mostly progesterone, which on its own, possible to maintain pregnancy
-17a (humans)
-20a (mice)
17b-estradiol (human)
inhibin A - promoters progesterone production
oxytocin - not too necessary
how is progesterone produced
pulsatile fashion - stimulation of hormone production from growing follicle and corpus dependent upon pituitary hormones, even before that, GnRH pulse generator
describe the difference between the delta-5 and delta-4 pathways
delta 5: affects theca and granuolsa cells, chol -> pregnenolone -> androgens -> estrogens in granulosa cell layer
delta-4: corpus luteum, side change cleavage of cholsterol in mitosis, conversion of pregnendone to progesterone, machinery does exist for production of estrogens and androgens though!
describe LH receptor signaling
stimulates progesterone mediated by LH actions via receptor
describe LH receptor signaling w/ StAR
LH binds to receptor, activates two secondary pathways of adenyl cyclase and cAMP vs. pKC
-target genes include progesterone receptor
-COX-2
StAR
LH switches from inducing estrogen TO progesterone
what is the role of StAR?
facilitates transport of cholesterol from outer mitochondriac membrane into inner mintochonrdiac membrane where cytochrome p450 side change cleaves makes cholesterol -> preg -> progesterone
why is StAR critical? has the method been found?
exact method, no, but it is known that StAR is critical in rate limiting movement of steroidogenesis
what are luteotrophins?
substances that promote survival of corpus luteum
primates: LH
nonprimates: luteotrophic complex of LH, prolactin, progesteron, and estrogen
describe the negative feedback in the corpus luteum
production of progesterone, and androgens and estradiol takes blood -> hypo/pituitary = negative effects and feedback
increased progesterone will change pulse generator function in freq/pulsativity
-downstream effects as far as pituitary secretion of LH, prog to estradiol ratio increases, pulsativity of GnRH decreases and favors LH secretion; we get mostly progesterone development, follicular development suppressed w/ low FSH
what is the role of high progesterone in follicular development?
blocks it
what is the role of progesterone on thermoregulatory centers?
thermogregulatory center in brain-basal body means temperature increases after production
describe luteolysis
at time of ovulation, lowering of high levels of estradiol and 2nd resurgence of corpus
- window of implantation b/t day 20-21
- absence of pregnancy -> luteolysis
fxnal regression - lowering of progesterone and StAR
structural regression - previously hypervascularized endocrinologically active glands begin to involute and form scar in ovarian cortex
primates: loss of luteotrophic support -> corups demise, LH pulsativity decreases, corpus becomes LESS receptive to LH, w/ LH receptor loss or downregulation. Injection pointless
nonprimates: luteolytic factor produced by endometrium, reaches ovary, causes corpus to regress
cell death by : apoptosis, autophagy, and necrosis
describe the experiment detailing luteolysis in nonprimates
mice have 2 uterine cords, did experiment w/ hystectomy so luteal phase prolonged, proving something in endometrium is responsible as luteolytic factor
what is PGF2-alpha?
luteolysin in nonprimates
- by various pathways, we get prostaglandin inclduing f2 alpha to cause vessel construction
- has receptor on luteal cell membrane - causes desensitization of LH receptor to block production of cAMP, and block prod of StAR, inactivates progesterone
molecular mechanism: oxytocin stimulates PGF2-alpha production, PGF2-alpha stimulates oxytocin
- progesteron stimulates PGF2 production, but endometrial oxytocin receptor initially, but prolonger progesterone decreases PR -> oxytocin receptor
- PGF@ decreases bloodflow -> endothelin
primates: aging of corpus, decreased stimulation of LH receptor/sensitivity means prog/estrogen levels drop
other mediators of luteolysis
inflammatory cascade, TNF-alpha, formation of corpus albicans (scar tissue)
describe the rescue of the corpus luteum: post-ovulation, if sperm present, fertilization occurs
takes many days for embryo to go from tubules to endometrium (6-20 days)
-implantation ensues - trophoblastic tissues starts to make hCG. Early placenta trophoblasts start making hCG and act on LH receptor, prog levels go up so corpus rescued
8-9 weeks: corpus ages, starts to die, but synctiotrophoblasts on their own produce lots of progesterone
describe miscarriage
corpus dies before placenta takes over, hemmoragghic
