Effect of estradiol on neurotransmitter sensitive adenylate cyclase. Its possible role in 'sexual differentiation'

Adenylate cyclase activity is lower in the hypothalamus of 5-day-old male rats than in females. This may be due to the presence of estradiol (E2) in this area of the male but not in the female since castration of the newborn male leads to an enzyme activity in the hypothalamus that is indistinguishable from that of the female and androgenization of the newborn female causes an enzyme activity level comparable to that of the male. In the adult, enzyme activity is highest when the concentration of E2 is at its lowest level; adenylate cyclase activity in the hypothalamus-preoptic area was found to be higher in the metestrus female than in proestrus or in the adult male. In vitro E2 was shown to reduce enzyme activity and this reduction was found to be dependent on induction of protein biosynthesis. In addition, there appears to be a requirement for Ca2+ in the E2-induced reduction of cyclase activity. Although F- activates the enzyme in all of the cases studied, the reduction in enzyme activity brought about by E2 is not reversed by F-, suggesting that the effect of E2 is not on the receptor. As sexual differentiation is brought about by the action of E2 during the first week after birth, it seems plausible to suggest that this interaction between hormone and enzyme is an early step in the sexual differentiation of the brain.