Placental production of 5 beta-pregnane-3 alpha,20 alpha-diol in goats

A major product of progesterone metabolism by the goat placenta in vitro was found to be 5 beta-pregnane-3 alpha,20 alpha-diol. The concentration of this steroid has been measured by radio-immunoassay in the peripheral circulation during pregnancy. Peripheral plasma concentrations of 5 beta-pregnane-3 alpha,20 alpha-diol were low (less than 6 nmol/l) in anoestrous and nonpregnant ovariectomized goats, and during the first month of pregnancy but increased progressively after day 45 of pregnancy, reaching 78-94 nmol/1 between days 112 and 142. Thereafter levels declined before term. Changes in the plasma concentration of 5 beta-pregnane-3 alpha,20 alpha-diol during pregnancy in the goat therefore resembled those of progesterone in the sheep. Plasma concentrations of 5 beta-pregnane-3 alpha,20 alpha-diol between day 70 and term were not influenced by repeated administration of medroxyprogesterone acetate from days 51 to 82 or by lutectomy in goats treated with medroxyprogesterone acetate. Secretion of 5 beta-pregnane-3 alpha,20 alpha-diol by the uterus and its contents was indicated by a positive venous-arterial difference across the uterus between days 128 and 141 in three ovariectomized pregnant goats receiving medroxyprogesterone acetate. Comparison of the rates of metabolism of progesterone by homogenates of placenta in vitro showed that the placental tissue from goats was three time more active in this respect than was tissue from sheep. The ratio of the plasma concentrations of 5 beta-pregnane-3 alpha,20 alpha-diol and progesterone in late pregnancy in ovariectomized or lutectomized goats exceeded by a factor of 10 that in sheep at a comparable stage of gestation. It is suggested that reductive metabolism of progesterone before it is secreted may account for the inability of the placenta to maintain pregnancy after ovariectomy in goats.