Roselli C E, Klosterman S A
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201-3098, USA.
Endocrinology. 1998 Jul;139(7):3193-201. doi: 10.1210/endo.139.7.6101.
Androgens regulate aromatase activity in the medial preoptic area and other components of the brain circuit that mediates male sexual behavior. The levels of aromatase activity within these brain regions are greater in males than in females. As the activation of copulation requires aromatization of testosterone to estradiol, this quantitative enzymatic difference between sexes could contribute to the greater behavioral response displayed by males. The present study was designed to test the hypothesis that gender differences in brain aromatase activity of adult rats are dependent on the sexual differentiation of the brain that occurs during perinatal exposure to gonadal hormones. Aromatase activity was measured in vitro in microdissected brain samples using a sensitive radiometric assay. We examined the effect of pre- and postnatal treatment with testosterone propionate or diethylstilbestrol on basal levels and androgen responsiveness of aromatase in adults. In addition, we examined what effect prepubertal gonadectomy exerts on enzyme regulation. Our results demonstrate that perinatal treatments with gonadal hormones that are known to differentiate sexual behavior can completely masculinize the capacity for aromatization in the adult female. The process that differentiates aromatase expression appears to depend on androgen exposure and, in part, local estrogen synthesis, as diethylstilbestrol was able to substitute for testosterone propionate. We also observed that prepubertal gonadectomy reduced the levels of aromatase activity measured in adult brain, suggesting that gonadal hormones that are secreted during puberty may enhance the expression of aromatase activity in adulthood. From this study, we conclude that testosterone and/or its estrogenic metabolites act on the developing brain to determine the gender-specific capacity for aromatization and to regulate androgen responsiveness within components of the neural circuitry that mediates male sexual behavior.
雄激素调节内侧视前区及介导雄性性行为的脑回路其他组成部分中的芳香化酶活性。这些脑区中的芳香化酶活性水平在雄性中高于雌性。由于交配的激活需要将睾酮芳香化为雌二醇，这种性别间的定量酶差异可能导致雄性表现出更强的行为反应。本研究旨在检验以下假设：成年大鼠脑芳香化酶活性的性别差异取决于围产期暴露于性腺激素期间发生的脑性分化。使用灵敏的放射测定法在体外对显微切割的脑样本中的芳香化酶活性进行测量。我们研究了产前和产后用丙酸睾酮或己烯雌酚处理对成年大鼠芳香化酶基础水平和雄激素反应性的影响。此外，我们研究了青春期前性腺切除对酶调节的作用。我们的结果表明，已知能分化性行为的围产期性腺激素处理可使成年雌性的芳香化能力完全男性化。分化芳香化酶表达的过程似乎取决于雄激素暴露，部分还取决于局部雌激素合成，因为己烯雌酚能够替代丙酸睾酮。我们还观察到青春期前性腺切除降低了成年脑测量的芳香化酶活性水平，表明青春期分泌的性腺激素可能增强成年期芳香化酶活性的表达。从这项研究中，我们得出结论，睾酮和/或其雌激素代谢产物作用于发育中的脑，以确定性别特异性的芳香化能力，并调节介导雄性性行为的神经回路组成部分内的雄激素反应性。
