67 INHIBITION OF 5α-REDUCTASE DURING LATE GESTATION IN THE MARE

Abstract

During the latter half of pregnancy in the mare, circulating concentrations of progesterone (P4) are low and a major bioactive progestogen, 5α-dihydroprogesterone (DHP), is present in high concentrations. DHP is formed through the activity of 5α-reductase, which converts P4 to DHP. Further metabolites of DHP have been attributed to fetal and myometrial quiescence. The purpose of this study was to examine the effects of a 5α-reductase inhibitor (dutasteride) on P4 metabolism and onset of parturition. Pregnant mares (n = 5) were treated with dutasteride (0.01 mg kg–1; IM), and control mares (n = 4) received vehicle alone from 300 to 320 days of gestation or until foaling. Serum concentrations of P4 and DHP were determined with liquid chromatography/tandem mass spectrometry (LC/MS-MS) daily for 9 days preceding parturition. Endocrine data were analysed with a random effects mixed model with time, treatment (TRT), and time × TRT interaction. Gestational data were analysed with a Wilcoxon test. Although there was a significant effect of time on P4 and DHP, there was no effect of TRT or time × TRT on these progestogens. For the ratio of DHP/P4, there were significant effects of time, TRT, and time × TRT interaction such that the ratio of DHP/P4 was greater in the control than dutasteride-treated mares. Birth weight and gestational length were not different (P > 0.2) between the dutasteride-treated and control mares, although placental weights were greater (P < 0.05) in dutasteride-treated mares. Because the ratio of DHP/P4 was suppressed in dutasteride-treated mares, it appears that dutasteride was active in late gestational mares. Although gestational length and neonatal weights were not different between groups, placentas from dutasteride-treated mares were heavier than those from control mares. The reason for the increase in placental weights was not determined.