MCDB 240: Ovary III

Question 1

define ovulation

Answer 1

preparation to switch to nurturing of embryo - luteal or progestric stage

Question 2

describe the results of the LH surge

Answer 2

1) rupture of follicle w/ release of egg
2) cumulus expansion
3) egg maturation

LH also important for lutenization, or formation of corpus luteum

Question 3

define luteinization

Answer 3

follicle physicall and structurally reorganized
-process of differentiation by which theca and granulosa cells become luteal cells. Results in formation of corpus luteum

Question 4

define the cell types of the corpus luteum

Answer 4

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

Question 5

define angiogenesis

Answer 5

de novo development of blood cells

Question 6

define the difference between follicle and the corpus

Answer 6

follicle before had basement membrane to separate theca from granulosa

Question 7

define luteal angiogenesis

Answer 7

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

Question 8

define the timeline of corpus development

Answer 8

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

Question 9

describe the homerrohagic corpus luteum

Answer 9

cyst forms, corpus fxn compromised to generate progesterone, ruptures in abdomen

Question 10

describe the luteal hormones

Answer 10

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

Question 11

how is progesterone produced

Answer 11

pulsatile fashion - stimulation of hormone production from growing follicle and corpus dependent upon pituitary hormones, even before that, GnRH pulse generator

Question 12

describe the difference between the delta-5 and delta-4 pathways

Answer 12

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!

Question 13

describe LH receptor signaling

Answer 13

stimulates progesterone mediated by LH actions via receptor

Question 14

describe LH receptor signaling w/ StAR

Answer 14

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

Question 15

what is the role of StAR?

Answer 15

facilitates transport of cholesterol from outer mitochondriac membrane into inner mintochonrdiac membrane where cytochrome p450 side change cleaves makes cholesterol -> preg -> progesterone

Question 16

why is StAR critical? has the method been found?

Answer 16

exact method, no, but it is known that StAR is critical in rate limiting movement of steroidogenesis

Question 17

what are luteotrophins?

Answer 17

substances that promote survival of corpus luteum

primates: LH
nonprimates: luteotrophic complex of LH, prolactin, progesteron, and estrogen

Question 18

describe the negative feedback in the corpus luteum

Answer 18

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

Question 19

what is the role of high progesterone in follicular development?

Answer 19

blocks it

Question 20

what is the role of progesterone on thermoregulatory centers?

Answer 20

thermogregulatory center in brain-basal body means temperature increases after production

Question 21

describe luteolysis

Answer 21

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

Question 22

describe the experiment detailing luteolysis in nonprimates

Answer 22

mice have 2 uterine cords, did experiment w/ hystectomy so luteal phase prolonged, proving something in endometrium is responsible as luteolytic factor

Question 23

what is PGF2-alpha?

Answer 23

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

Question 24

other mediators of luteolysis

Answer 24

inflammatory cascade, TNF-alpha, formation of corpus albicans (scar tissue)

Question 25

describe the rescue of the corpus luteum: post-ovulation, if sperm present, fertilization occurs

Answer 25

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

Question 26

describe miscarriage

Answer 26

corpus dies before placenta takes over, hemmoragghic