Steroid synthesis is required for pregnancy maintenance and for parturition, but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to (1) determine placental enzyme activity, progesterone, and estradiol measured by immunoassay in late gestation ewes on low-, moderate-, and high-nutritional planes, (2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude that (1) diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and (2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.
|Number of pages||9|
|Journal||Biology of Reproduction|
|State||Published - Sep 1 2018|
Bibliographical noteFunding Information:
: The authors would like to acknowledge the financial support of a USDA-NIFA-AFRI seed grant, no. 2013-67016-20963 and the staff at the Equine Analytical Laboratory, School of Veterinary Medicine, University of California, Davis, for their kind help and expert technical assistance. We thank the Animal Nutrition and Physiology Center, the Sheep Unit, and the Physiology Laboratory of the Department of Animal Sciences, NDSU, for their assistance with the animal husbandry, tissue collections, and laboratory analyses, and Matthew S. Crouse for help with statistical analysis.
1Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, North Dakota, USA; 2Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA and 3Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA ∗Correspondence: Department of Population Health & Reproduction, School of Veterinary Medicine, 1089 Veterinary Medicine Drive, 3223 VM3B, University of California, Davis, CA 95616, USA. E-mail: firstname.lastname@example.org †Grant Support: The authors would like to acknowledge the financial support of a USDA-NIFA-AFRI seed grant, no. 2013-67016-20963 and the staff at the Equine Analytical Laboratory, School of Veterinary Medicine, University of California, Davis, for their kind help and expert technical assistance. Edited by Dr. Romana Nowak, PhD, University of Illinois Urbana-Champaign.
© The Author(s) 2018.
ASJC Scopus subject areas
- Reproductive Medicine
- Cell Biology