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The Luteal Phase of the Estrous and Menstrual Cycle. John Parrish. steroid synthesis progesterone collagenase theca interna. present 1-3 days following ovulation blood vessels in follicle wall rupture walls collapse cells intermix old basement membrane becomes connective tissue of CL.
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The Luteal Phase of the Estrous and Menstrual Cycle John Parrish
steroid synthesis • progesterone • collagenase • theca interna
present 1-3 days following ovulation • blood vessels in follicle wall rupture • walls collapse • cells intermix • old basement membrane becomes connective tissue of CL
increases in size • papilla forms • composed of cells from the granulosa and theca interna • progesterone production increases • a small cavity may be present where the folliclular antrum was present
Luteal Tissue • Large cells from granulosa • Small cells from the theca interna
Mitochondria Secretory Granules - Oxytocin - Relaxin
Functional Capability of CL • the number of luteal cells • large cells undergo hypertrophy (3 fold) • small cells undergo hyperplasia (5 fold) • vascularization of CL • Initiated by angiogenic factors from follicle • Vascularity effects CL steroid synthesis and delivery of hormones • Insufficient CL function • Failure to maintain pregnancy • Important in domestic animals
Blocks Estrus Negative Feedback Progesterone Targets Aveolar Development
LH Adenylate Cyclase cAMP cAMP Progesterone ATP Histones Nucleus DNA mRNA Molecular Mechanism of LH on Luteal Cell (cAMP second messenger) G Plasma Membrane Receptor PKA R C S-ER Steroid Synthesis (+ PO4) Mitochondria Cholesterol Pregnenolone Cholesterol Protein R-ER Protein Synthesis Synthesis (Enzymes)
LH Chol Chol LDL LDL Adenylate Cyclase cAMP cAMP Progesterone ATP Molecular Mechanism of LH on Luteal Cell (cAMP second messenger) G Plasma Membrane Receptor PKA R C S-ER Steroid Synthesis Chol-Ester (+ PO4) LDL Mitochondria Chol Esterase Cholesterol Pregnenolone Cholesterol Protein R-ER Protein Synthesis Synthesis (Enzymes)
Luteolysis • Uterus • PGF2a • Oxytocin
Luteolysis in Cows, Ewes, Sows NormalUterus TotalHysterectomy CL CL LifespanLonger CL Normal Lifespan Similar to Gestation Length ContralateralHysterectomy IpsilateralHysterectomy CL LifespanLonger CL Normal Lifespan >35 days
Luteolysis • Uterus • PGF2a • Oxytocin
Prostaglandin synthesis by uterine endometrium is released into the uterine vein. Prostaglandin F2a Control of Luteolysis Uterine Horn Progesterone from CL stimulates production of uterine PGF2a after day 15 in cow Corpus Luteum Oviduct Ovary Uterine Vein Ovarian Pedicle PGF PGF2a is picked up by ovarian artery through counter current exchange and delivered back to the ovary where it causes lysis of the CL PGF into Artery Uterine Artery
NormalUterus TotalHysterectomy CL CL NormalLifespan CL Maintained Luteolysis Mare ContralateralHysterectomy IpsilateralHysterectomy 50% of CL’s Maintained 50% of CL’s Maintained
PGF Not Effective (Sow) PGF Not Effective (Cow, Ewe, Mare)
Luteolysis • Uterus • PGF2a • Oxytocin
Oxytocin PGF2a Relationship of Oxytocin and PGF2a Posterior Pituitary Anterior Pituitary CL Ovary Uterus
Luteolysis • decreased blood flow • cellular response • apoptosis • progesterone synthesis • Immune response • Lymphocytes • Macrophages
Ca2+ DAG PIP2 PIP2 G-protein PLC Protein Kinase C IP3 Ca2+ R R Molecular Mechanism of PGF(Ca2+ Second Messenger) PGF Plasma Membrane Receptor Cholesterol Ca2+ Endoplasmic Reticulum Apoptosis Progesterone Plasma Membrane
Luteolysis • decreased blood flow • cellular response • apoptosis • progesterone synthesis • Immune response • Lymphocytes • Macrophages
Recruitment Recruitment Anterior Pituitary Hormones LH FSH Progesterone Ovarian Hormones Estradiol Ovulation Corpus Albicans Follicle Corpus Luteum Ovary Dominance Selection Uterine Endo- metrium 2 4 6 8 10 12 14 16 18 20 22 24 26 28 2
Luteolysis in the Primate • Does not require the uterus • CL lifespan in the human is 12-14 days unless pregnancy occurs • In the absence of pregnancy, CL self destructs • Possible intra-ovarian oxytocin receptors and PGF2a production • Menstruation • Drop in P4 and E2 • Endometrial PGF2a, vasoconstriction, necrosis • Endometrial inflammation and tissue degeneration