Progestagen metabolites in fetal sheep plasma: the effect of fetal nephrectomy

Fetal sheep (100-115 days gestation) were surgically implanted with femoral arterial and venous cannulae and then either sham-operated (control) or bilaterally nephrectomized. Following a 5-day recovery period, fetal blood samples (10 ml/48 h) were taken and the steroid sulphate fraction analysed as trimethylsilyl esters by gas-liquid chromatography (g. l.c.). Three progestagen metabolites were repeatedly detected in plasma samples from control and nephrectomized fetuses and identified by g.l.c.-mass-spectrometric techniques as 5 beta-pregnane-3 beta,20 beta-diol, 5 beta-pregnane-3 beta,20 alpha-diol and 5 beta-pregnane-3 alpha,20 alpha-diol. In three control fetuses the plasma concentration of both 5 beta-pregnane-3 beta,20 beta-diol and -20 alpha-diol showed a steady increase from about 0.5 micrograms/ml at 105 days to about 1.5 and 2-2.5 micrograms/ml, respectively, at 143 days gestation. A study in one fetus indicated that the values then fell precipitously by term (147 days) as plasma cortisol concentrations rose. In contrast, whilst no consistent patterns were seen in their concentration in five nephrectomized fetuses the levels were 2-10 times higher than the control values (0.5-10 micrograms/ml) at all stages. The plasma concentration of 5 beta-pregnane-3 alpha,20 alpha-diol was less perturbed by nephrectomy and only showed a slight increase over control values (0.2-0.5 micrograms/ml). Three sham-operated fetuses which aborted following infection also showed increased plasma concentrations of 5 beta-pregnane-3 beta,20 beta-diol and -20 alpha-diol, similar to the nephrectomized fetuses. It is postulated that high levels of circulating progesterone metabolites may reflect induced increases in adrenal endocrine activity culminating in premature activation of those changes in adrenal function which trigger parturition.