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Luteal Phase Corpus Luteum corpus hemorrhagicum (ovulation till day 1 to 3) o CL becomes more recognizable by day 3 to 5 production of progesterone o size of CL corresponds with its progesterone production luteolysis o regression of CL o change in structure as well as ability to secret progesterone o the CL becomes the corpus albicans o Corpus Luteum Formation in response to LH surge, granulosa and theca cells of preovulatory follicle luteinize basement membrane disintergrates at ovulation the walls of the follicle collapse theca and granulosa cells mix basement membrane becomes the connective tissue network of CL breakage of small blood vessels leads to the blood clot seen in the corpus hemorrhagicum CL structure and Function large luteal cells from granulosa o contain secretory granules during estrous cycle contain oxytocin during pregnancy contain relaxin small luteal cells from theca interna o do not contain secretory granules both small and large luteal cells make progesterone increase in CL size due to o large luteal cells increase in size (hypertrophy) o small cells increase in number (hyperplasia) vascularization of CL insufficient luteal function important factor in reproductive failure Targets of Progesterone Action hpothalamus o o o negative feedback on GnRH amplitude and frequency prevents behavioral estrus stops preovulatory LH surge uterus endometrium stimulates endometrial gland secretion which supports development of conceptus prior to implantation o myometrium decreases muscle contraction (motility) mammary gland o stimulates development of alveoli o Progesterone Synthesis Cholesterol ester is importated into the cell bound to LDL LH via its binding to its receptor increases cAMP and PKA PKA causes o increase internalization of the cholesterol-LDL molecule o activates cholesterol esterase o increased cholesterol uptake by mitochondria o probably a role in regulating pregnenolone conversion to progesterone in smooth ER Luteolysis uterus required o hysterectomy prevents luteolysis o partial hysterectomy ipsilateral prevents luteolysis contralateral no effect on luteolysis, occurs at normal time o transplant ovary to neck prevents luteolysis o uterus needed for luteolysis and must be near ovary to have effect PGF is luteolysin o counter current exchange between uterine vein and ovarian artery present in cow, ewe, sow important as PGF is destroyed in peripheral circulation as it passes through the lungs not present in mare PGF gets to ovary after going through the general circulation mare ovary is more sensitive to PGF than other species o sensitivity of CL to PGF cow, ewe only after day 5-6 of cycle sow not until day 12-14 of cycle oxytocin o produced by CL (large luteal cells) o receptors in uterus decline after ovulation as progesterone increases o after 10-12 days progesterone, uterine oxytocin receptors again begin to increase o in response to oxytocin binding to its receptor in the uterine endometrium, PGF is released o PGF triggers release of oxytocin from CL to intiate a positive feedback loop o oxytocin can also come from posterior pituitary intracellular mechanisms of luteolysis o ischemia (decreased blood flow to CL) o apoptosis increase in intracellular calcium protein kinase C inhibits progesterone synthesis the immune system o macrophages and lymphocytes are present in luteal tissue and increase at the time of luteolysis can perform phagocytosis of luteal cells cytokines are released and cause cell death stop progesterone production apoptosis