1. The Luteal Phase of the Estrous and Menstrual Cycle John Parrish

3. steroid synthesis –progesterone collagenase –theca interna

4. present 1-3 days following ovulation blood vessels in follicle wall rupture walls collapse cells intermix old basement membrane becomes connective tissue of CL

5. 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

6. Luteal Tissue Large cells from granulosa Small cells from the theca interna Large cells from granulosa Small cells from the theca interna

8. Mitochondria Secretory Granules - Oxytocin - Relaxin

9. 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 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

10. Progesterone Targets Aveolar Development Blocks Estrus Negative Feedback

11. Molecular Mechanism of LH on Luteal Cell Receptor PKA Nucleus DNA Histones Protein Synthesis (Enzymes) mRNA Plasma Membrane (cAMP second messenger) Cholesterol G Adenylate Cyclase C R cAMP LH ATP cAMP (+ PO 4 ) R-ER Protein Synthesis Mitochondria Cholesterol Pregnenolone S-ER Steroid Synthesis Progesterone

12. Molecular Mechanism of LH on Luteal Cell Receptor PKA Protein Synthesis (Enzymes) Plasma Membrane (cAMP second messenger) Cholesterol G Adenylate Cyclase C R cAMP LH ATP cAMP (+ PO 4 ) R-ER Protein Synthesis Mitochondria Cholesterol Pregnenolone S-ER Steroid Synthesis Progesterone Chol LDL Chol LDL Chol-Ester LDL Chol Esterase

13. Luteolysis Uterus PGF 2  Oxytocin Uterus PGF 2  Oxytocin

14. Luteolysis in Cows, Ewes, Sows Total Hysterectomy Ipsilateral Hysterectomy Contralateral Hysterectomy Normal Uterus CL CL Normal Lifespan CL Lifespan Longer Similar to Gestation Length >35 days

15. Luteolysis Uterus PGF 2  Oxytocin Uterus PGF 2  Oxytocin

16. Prostaglandin F2  Control of Luteolysis Progesterone from CL stimulates production of uterine PGF2  after day 15 in cow Uterine Horn Uterine Vein Prostaglandin synthesis by uterine endometrium is released into the uterine vein. Oviduct Ovary Corpus Luteum PGF2  is picked up by ovarian artery through counter current exchange and delivered back to the ovary where it causes lysis of the CL Uterine Artery Ovarian Pedicle PGF PGF into Artery

17. Luteolysis Mare Total Hysterectomy Ipsilateral Hysterectomy Contralateral Hysterectomy Normal Uterus CL CL Normal Lifespan 50% of CL’s Maintained CL Maintained 50% of CL’s Maintained

18. Blood Supply to Uterus and Ovary in the Mare

19. PGF Not Effective (Cow, Ewe, Mare) PGF Not Effective (Sow)

20. Luteolysis Uterus PGF 2  Oxytocin Uterus PGF 2  Oxytocin

23. Relationship of Oxytocin and PGF2  Uterus Ovary CL PGF2  Anterior Pituitary Posterior Pituitary Oxytocin

24. Luteolysis decreased blood flow cellular response –apoptosis –progesterone synthesis Immune response –Lymphocytes –Macrophages decreased blood flow cellular response –apoptosis –progesterone synthesis Immune response –Lymphocytes –Macrophages

25. Molecular Mechanism of PGF (Ca 2+ Second Messenger) PLC PIP 2 Endoplasmic Reticulum Ca 2+ Protein Kinase C Plasma Membrane PGF Receptor G-protein DAG IP 3 R Ca 2+ Plasma Membrane Ca 2+ R PIP 2 Cholesterol Progesterone Apoptosis

26. Luteolysis decreased blood flow cellular response –apoptosis –progesterone synthesis Immune response –Lymphocytes –Macrophages decreased blood flow cellular response –apoptosis –progesterone synthesis Immune response –Lymphocytes –Macrophages

27. Menstrual Cycle

28. FSH LH Estradiol Progesterone Follicle Ovulation Corpus Luteum Corpus Albicans 2468101416182022242628212 Anterior Pituitary Hormones Ovarian Hormones Ovary Uterine Endo- metrium Recruitment Selection Dominance Recruitment

29. 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 PGF 2  production Menstruation –Drop in P 4 and E 2 –Endometrial PGF 2 , vasoconstriction, necrosis –Endometrial inflammation and tissue degeneration