Production of 5 alpha-dihydroprogesterone during late pregnancy in the mare

Changes in the progesterone metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) in maternal plasma in late gestation, and possible sites of production of this steroid were studied in pony and Thoroughbred mares by an enzyme-linked immunosorbant assay for 5 alpha-DHP. In Thoroughbred mares, plasma 5 alpha-DHP increased from 63.7 +/- 10.5 ng/ml (27 days pre-partum) to 161.7 +/- 30.8 ng/ml (1 day pre-partum) falling to 90.2 +/- 16.1 ng/ml on the day of parturition. In pony mares, values rose from 30.8 +/- 8.1 ng/ml (27 days pre-partum) to 79.1 +/- 30.8 ng/ml (3 days pre-partum) and then decreased to 28.2 +/- 7.1 ng/ml on the day of parturition. Concentrations of 5 alpha-DHP were greater in the umbilical and uterine veins than in the corresponding umbilical and uterine artery samples. Tissues incubated with isotopically-labelled substrates showed that the fetal placenta converted pregnenolone to progesterone (47.5 +/- 9.0%). Endometrium metabolised [3H]pregnenolone to progesterone and 5 alpha-DHP (11.0 +/- 3.0% and 7.8 +/- 2.4%, respectively), and [14C]progesterone to 5 alpha-DHP (9.3 +/- 2.5%). Deuterium-labelled substrates were used to confirm the identity of these products by gas chromatography-mass spectrometry. Negligible amounts of 5 alpha-DHP were formed by other fetal tissues (adrenal, liver, kidney and testis). The results show that 5 alpha-DHP production in late pregnancy is derived primarily from endometrial metabolism of pregnenolone and/or progesterone.