EFFECT OF ANDROSTENEDIONE ADMINISTRATION ON THE MATERNAL HYPOTHALAMO-PITUITARY-ADRENO-PLACENTAL AXIS IN THE PREGNANT RHESUS-MONKEY

To assess the interaction among androgens, placenta, and the hypothala mo-pituitary-adrenal axis we studied effects of androstenedione admini stered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) w ere instrumented under general halothane anesthesia with maternal femo ral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples f or CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken a t 1.5-h intervals for 7 h starting 2 h before darkness. On the followi ng day, a continuous iv androstenedione infusion (0.3 mg/kg(.)min at 0 .25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days afte r androstenedione or vehicle administration. Maternal plasma CRH, ACTH , DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase i n maternal plasma estradiol and a sustained fall in maternal plasma AC TH, but did not affect maternal plasma CRH, DHEAS, or cortisol concent rations. These results provide evidence for negative feedback regulati on by androgens at the hypothalamo-pituitary-adrenal axis in the pregn ant monkey. Lack of inhibition of maternal plasma CRH after androstene dione administration supports differential regulation of hypothalamic and placental CRH by androgens.