title: Progestin withdrawal at parturition in the mare.
abstract: Mammalian pregnancies need progestogenic support and birth requires progestin withdrawal. The absence of progesterone in pregnant mares, and the progestogenic bioactivity of 5α-dihydroprogesterone (DHP), led us to reexamine progestin withdrawal at foaling. Systemic pregnane concentrations (DHP, allopregnanolone, pregnenolone, 5α-pregnane-3β, 20α-diol (3β,20αDHP), 20α-hydroxy-5α-dihydroprogesterone (20αDHP)) and progesterone) were monitored in mares for 10days before foaling (n=7) by liquid chromatography-mass spectrometry. The biopotency of dominant metabolites was assessed using luciferase reporter assays. Stable transfected Chinese hamster ovarian cells expressing the equine progesterone receptor (ePGR) were transfected with an MMTV-luciferase expression plasmid responsive to steroid agonists. Cells were incubated with increasing concentrations (0-100nM) of progesterone, 20αDHP and 3α,20βDHP. The concentrations of circulating pregnanes in periparturient mares were (highest to lowest) 3α,20βDHP and 20αDHP (800-400ng/mL respectively), DHP and allopregnanolone (90 and 30ng/mL respectively), and pregnenolone and progesterone (4-2ng/mL). Concentrations of all measured pregnanes declined on average by 50% from prepartum peaks to the day before foaling. Maximum activation of the ePGR by progesterone occurred at 30nM; 20αDHP and 3α,20βDHP were significantly less biopotent. At prepartum concentrations, both 20αDHP and 3α,20βDHP exhibited significant ePGR activation. Progestogenic support of pregnancy declines from 3 to 5days before foaling. Prepartum peak concentrations indicate that DHP is the major progestin, but other pregnanes like 20αDHP are present in sufficient concentrations to play a physiological role in the absence of DHP. The authors conclude that progestin withdrawal associated with parturition in mares involves cessation of pregnane synthesis by the placenta.
authors: Department of Population Health and ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA.
authors: Erin L
authors: EL
authors: Legacki
authors: Department of Population Health and ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA.
authors: C J
authors: CJ
authors: Corbin
authors: Gluck Equine Research CenterDepartment of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: B A
authors: BA
authors: Ball
authors: Gluck Equine Research CenterDepartment of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: M
authors: M
authors: Wynn
authors: Gluck Equine Research CenterDepartment of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: S
authors: S
authors: Loux
authors: Department of Molecular BiosciencesSchool of Veterinary Medicine, University of California, Davis, California, USA.
authors: S D
authors: SD
authors: Stanley
authors: Department of Population Health and ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA ajconley@ucdavis.edu.
authors: A J
authors: AJ
authors: Conley
mesh_terms: D000818:Animals; D005260:Female; D006736:Horses; D006801:Humans; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D011284:Pregnenolone / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011372:Progestins / Q000172:deficiency*; D028761:Withholding Treatment
chemical_list: D011372:Progestins; D011374:Progesterone; D011284:Pregnenolone