Nuclear accumulation of estradiol derived from the aromatization of testosterone is inhibited by hypothalamic beta-receptor stimulation in the neonatal female rat.

We previously reported that hypothalamic beta-adrenergic receptor stimulation prevents testosterone (T)-induced androgenization (defeminization) of the female neonatal rat hypothalamus. It was hypothesized that hypothalamic beta-receptor stimulation blocks androgenization by reducing the nuclear accumulation of estradiol (E2) derived from the aromatization ofT. Various adrenergic agonists and antagonists were injected intracerebrally in 4-day-old female rats. I3HIT and its 3H-metabolites (including E2) were extracted from hypothalamic nuclear pellets, and separated from one another with thin-layer chromatography and/or Celite chromatography. The ratio of recovered 1� HIT and E3 in the control groups was arbitrarily assigned as a 100% conversion and nuclear accumulation. Phenoxybenzamine, an alpha-antagonist, and isoproterenol and isoxsuprine, beta-agonists, inhibited the nuclear accumulation of E3 to 66.7%, 69.0% and 85.0% of control, respectively. A nonadrenergic, specific, competitive aromatase inhibitor, 1,4,6androstratrien-3 .1 7-dione (ATD) inhibited aromatization (and subsequent nuclear accumulation) to 39.0% of control. The beta-antagonist, hydroxybenzylpindolol, specifically prevented the inhibition of nuclear accumulation produced by phenoxybenzamine, isoproterenol and isoxsuprine, but did not alter the inhibition of aromatization produced by AID. These studies support the hypothesis that beta-receptor stimulation prevents androgen�,zation of the brain by inhibiting either the aromatization ofT to E2 or the nuclear uptake of E2.