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 of T. Various adrenergic agonists and antagonists were injected intracerebrally in 4-day-old female rats. [3H] T 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 [3H] T and E2 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 E2 to 66.7%, 69.0% and 85.0% of control, respectively. A nonadrenergic, specific, competitive aromatase inhibitor, 1,4,6-androstratrien-3,17-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 ATD. These studies support the hypothesis that beta-receptor stimulation prevents androgenization of the brain by inhibiting either the aromatization of T to E2 or the nuclear uptake of E2.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D013739:Testosterone; D004958:Estradiol