Distribution and ovarian control of progestin-metabolizing enzymes in various rat hypothalamic regions

The three principal hypothalamic progesterone metabolizing enzyme activities, namely the progesterone 5α-reductase and 5α-dihydroprogesterone NADH- and NADPH-linked 3α-hydroxysteroid oxidoreductase (3α-HSOR) activities, were examined in discrete rat hypothalamic subsections throughout the estrous cycle and from ovariectomized rats treated with estradiol benzoate or vehicle. The regions studied included the median eminence, the medial preoptic area and the ventromedial and arcuate nuclei. The enzyme assays were performed using radiolabeled steroid substrates and reverse isotopic dilution analysis. While all four hypothalamic regions obtained from intact cycling animals possessed substantial amounts of these three enzyme activities, the median eminence generally had the highest activity levels (2- to 4-fold greater) except during estrus. The other three regions usually had comparable levels. No significant fluctuations were observed in any enzyme activity over the estrous cycle. After ovariectomy, there was a significant decrease (~ 35%) in the level of the NADPH-linked 3α-HSOR activity in the median eminence compared to the level observed in intact cycling animals, suggesting ovarian control. Estrogen treatment for 3 days did not restore this enzyme level to that observed in intact animals. The NADPH-linked 3α-HSOR activity from the other three hypothalamic regions, as well as the NADH-linked 3α-HSOR and the 5α-reductase activities from all four brain regions, did not change significantly after ovariectomy. These results indicate that the median eminence possesses an increased capacity for progesterone metabolism relative to the other hypothalamic regions tested, and that the NADPH-linked 3α-HSOR activity in this region may be under ovarian control.