CHANGES IN PITUITARY, HYPOTHALAMIC AND BRAIN PROGESTIN-METABOLIZING ENZYME-ACTIVITIES DURING LACTATION

Progesterone 5alpha-reductase activity and 5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) activities (NADH- and NADPH-linked) were measured in anterior pituitaries, hypothalami and brains from lactating rats (8 and 21 days postpartum) and non-lactating (60-day-old cycling) rats. Tissue levels of these three enzyme activities varied significantly among the three groups examined. In terms of pituitary, mean levels of both of its 3alpha-HSOR activities were 40-140% higher in actively lactating rats (8 days postpartum) relative to mean levels in lactating rats at weaning (21 days postpartum) or in nonlactating rats. There were no differences in pituitary progesterone 5alpha-reductase activity among the three experimental groups. In the hypothalamus, the NADPH-linked 3alpha-HSOR was elevated (50%) at 8 days of lactation compared to the group at 21 days. Hypothalamic NADH-linked 3alpha-HSOR levels did not vary among the 3 groups. Hypothalamic progesterone 5alpha-reductase levels in the actively lactating and weaning groups were 30% lower than those of the non-lactating group. Brain levels of progesterone 5alpha-reductase were also lower in these two lactating groups (35-55%) as compared to the non-lactating control group. In brain, NADPH 3alpha-HSOR activity did not vary among the three groups, but levels of NADH 3alpha-HSOR activity were lower (40-50%) in the weaning group as compared to the actively lactating and control groups. These findings suggest the possibility that tissue changes in these progesterone-metabolizing enzyme activities during lactation and at weaning are influencing the in situ supply of 3alpha,5alpha-tetrahydroprogesterone and 5alpha-dihydroprogesterone and their derivative effects on GABA(A) receptor activity and prolactin and gonadotropin release. The decreased activity of progesterone 5alpha-reductase in hypothalamus and brain would presumably reduce in situ 5alpha-dihydroprogesterone formation while increases in 3alpha-HSOR activity would suggest higher in situ 3alpha, 5alpha-tetrahydroprogesterone formation, especially in the pituitary.