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 [1β-³H]androstenedione as an index of estrogen formation. Aromatase activity was significantly greater in T-treated HPOA versus controls (P < 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. OVX-ADX hosts were either sham-operated or implanted with T-filled silastic capsules. Aromatase activity was much higher than in 8-week transplants, and T treatment again resulted in significantly enhanced levels versus controls (P < 0.01). There was no effect of the sex of the fetal donor. These results indicate that both basal levels and the androgen sensitivity of aromatase will develop in the rat HPOA of both sexes without exposure to gonadal steroids after E17, and without the influence of neural inputs to the HPOA. In addition, they establish that the mechanism of androgenic modulation of HPOA aromatase is functional in the late embryonic period.