PMID- 30763279 OWN - NLM STAT- MEDLINE DCOM- 20200501 LR - 20200501 IS - 1741-7899 (Electronic) IS - 1470-1626 (Linking) VI - 157 IP - 5 DP - 2019 May TI - Serum and tissue pregnanes and pregnenes after dexamethasone treatment of cows in late gestation. PG - 413-422 LID - 10.1530/REP-18-0558 [doi] AB - Dexamethasone (DEX) initiates parturition by inducing progesterone withdrawal and affecting placental steroidogenesis, but the effects of DEX in fetal and maternal tissue steroid synthetic capacity remains poorly investigated. Blood was collected from cows at 270 days of gestation before DEX or saline (SAL) treatment, and blood and tissues were collected at slaughter 38 h later. Steroid concentrations were determined by liquid chromatography tandem mass spectrometry to detect multiple steroids including 5alpha-reduced pregnane metabolites of progesterone. The activities of 3beta-hydroxysteroid dehydrogenase (3betaHSD) in cotyledonary and luteal microsomes and mitochondria and cotyledonary microsomal 5alpha-reductase were assessed. Quantitative PCR was used to further assess transcripts encoding enzymes and factors supporting steroidogenesis in cotyledonary and luteal tissues. Serum progesterone, pregnenolone, 5alpha-dihydroprogesterone (DHP) and allopregnanolone (3alphaDHP) concentrations (all <5 ng/mL before treatment) decreased in cows after DEX. However, the 20alpha-hydroxylated metabolite of DHP, 20alphaDHP, was higher before treatment ( approximately 100 ng/mL) than at slaughter but not affected by DEX. Serum, cotyledonary and luteal progesterone was lower in DEX- than SAL-treated cows. Progesterone was >100-fold higher in luteal than cotyledonary tissues, and serum and luteal concentrations were highly correlated in DEX-treated cows. 3betaHSD activity was >5-fold higher in luteal than cotyledonary tissue, microsomes had more 3betaHSD than mitochondria in luteal tissue but equal in cotyledonary sub-cellular fractions. DEX did not affect either luteal or cotyledonary 3betaHSD activity but luteal steroidogenic enzyme transcripts were lower in DEX-treated cows. DEX induced functional luteal regression and progesterone withdrawal before any changes in placental pregnene/pregnane synthesis and/or metabolism were detectable. FAU - Conley, Alan J AU - Conley AJ AD - Department of Population Health & Reproduction, University of California, Davis, California, USA. FAU - Legacki, Erin L AU - Legacki EL AD - Department of Population Health & Reproduction, University of California, Davis, California, USA. FAU - Corbin, C Jo AU - Corbin CJ AD - Department of Population Health & Reproduction, University of California, Davis, California, USA. FAU - Stanley, Scott AU - Stanley S AD - Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA. FAU - Dahlen, Carl R AU - Dahlen CR AD - Center for Nutrition and Pregnancy and Department of Animal Sciences, North Dakota State University, Fargo, North Dakota, USA. FAU - Reynolds, Lawrence P AU - Reynolds LP AD - Center for Nutrition and Pregnancy and Department of Animal Sciences, North Dakota State University, Fargo, North Dakota, USA. LA - eng PT - Journal Article PT - Randomized Controlled Trial, Veterinary PL - England TA - Reproduction JT - Reproduction (Cambridge, England) JID - 100966036 RN - 0 (Pregnanes) RN - 0 (Pregnenes) RN - 4G7DS2Q64Y (Progesterone) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - *Cattle/metabolism MH - Corpus Luteum/drug effects/metabolism MH - Dexamethasone/*pharmacology MH - Female MH - Fetus/drug effects/metabolism MH - Gestational Age MH - Luteolysis/blood/drug effects/metabolism MH - Parturition/*drug effects/metabolism MH - Pregnancy MH - *Pregnancy, Animal/blood/drug effects/metabolism MH - Pregnanes/blood/*metabolism MH - Pregnenes/blood/*metabolism MH - Progesterone/metabolism EDAT- 2019/02/15 06:00 MHDA- 2020/05/02 06:00 CRDT- 2019/02/15 06:00 PHST- 2018/10/26 00:00 [received] PHST- 2019/02/14 00:00 [accepted] PHST- 2019/02/15 06:00 [pubmed] PHST- 2020/05/02 06:00 [medline] PHST- 2019/02/15 06:00 [entrez] AID - REP-18-0558.R2 [pii] AID - 10.1530/REP-18-0558 [doi] PST - ppublish SO - Reproduction. 2019 May;157(5):413-422. doi: 10.1530/REP-18-0558.