Modulation of aromatase activity by testosterone in transplants of fetal rat hypothalamus-preoptic area.

Conversion of androgens to estrogens by neural aromatase appears to be a prerequisite for a variety of effects of androgens on brain function, including sexual differentiation. Activity of aromatase is modulated by its substrate testosterone (T) in adult hypothalamus-preoptic area (HPOA), resulting in significantly higher levels in the male. Perinatal sex differences in activity have also been observed in hypothalamus, POA and/or amygdala. However, it is not known if higher levels in the perinatal male occur in response to circulating androgens, nor whether early exposure to gonadal steroids is necessary to establish either basal levels or the androgen sensitivity of aromatase activity in the adult brain. In order to investigate the influence of early steroid exposure on the development of neural aromatase activity, embryonic day (E)17 fetal HPOA was transplanted onto the choroidal pia overlying the superior colliculus of adult ovariectomized-adrenalectomized (OVX-ADX) Holtzman female hosts. In the first experiment, the effect of androgen exposure on aromatase activity in mature HPOA transplants was determined. Hosts received T-filled silastic capsules or underwent sham surgery 7 weeks after transplantation and were sacrificed 7 days later. Aromatase activity was determined in vitro using the stereospecific production of 3H2O from [1 beta-3H]androstenedione as an index of estrogen formation. Aromatase activity was significantly greater in T-treated HPOA versus controls (P less than 0.005). Activity was not affected by the sex of the donor fetus. In the second experiment, the effect of androgen exposure during the first 6 days following transplantation of E17 HPOA (corresponding to the last gestational week) was determined.(ABSTRACT TRUNCATED AT 250 WORDS)