Roselli C E, Resko J A
Department of Physiology, Oregon Health Sciences University, Portland 97201.
J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):499-508. doi: 10.1016/0960-0760(93)90254-t.
The intracellular conversion of testosterone to estradiol by the aromatase enzyme complex is an important step in many of the central actions of testosterone. In rats, estrogen given alone, or in combination with dihydrotestosterone, mimics most of the behavioral effects of testosterone, whereas treatment with antiestrogens or aromatase inhibitors block facilitation of copulatory behavior by testosterone. We used a highly sensitive in vitro radiometric assay to analyze the distribution and regulation of brain aromatase activity. Studies using micropunch dissections revealed that the highest levels of aromatase activity are found in an interconnected group of sexually dimorphic nuclei which constitutes a neural circuit important in the control of male sexual behavior. Androgen regulated aromatase activity in many diencephalic nuclei, including the medial preoptic nucleus, but not in the medial and cortical nuclei of the amygdala. Additional genetic evidence for both androgen-dependent and -independent control of brain AA was obtained by studies of androgen-insensitive testicular-feminized rats. These observations suggest that critical differences in enzyme responsiveness are present in different brain areas. Within several nuclei, sex differences in aromatase induction correlated with differences in nuclear androgen receptor concentrations suggesting that neural responsiveness to testosterone is sexually differentiated. Estradiol and dihydrotestosterone acted synergistically to regulate aromatase activity in the preoptic area. In addition, time-course studies showed that estrogen treatment increased the duration of nuclear androgen receptor occupation in the preoptic area of male rats treated with dihydrotestosterone. These results suggest possible ways that estrogens and androgens may interact at the cellular level to regulate neural function and behavior.
芳香化酶复合物将睾酮细胞内转化为雌二醇是睾酮许多中枢作用中的重要一步。在大鼠中，单独给予雌激素或与双氢睾酮联合给予时，可模拟睾酮的大多数行为效应，而用抗雌激素或芳香化酶抑制剂治疗可阻断睾酮对交配行为的促进作用。我们使用一种高度敏感的体外放射性测定法来分析脑芳香化酶活性的分布和调节。使用微量打孔解剖的研究表明，在一组相互连接的性二态核中发现了最高水平的芳香化酶活性，这构成了在控制雄性性行为中起重要作用的神经回路。雄激素调节许多间脑核中的芳香化酶活性，包括内侧视前核，但不调节杏仁核的内侧核和皮质核。通过对雄激素不敏感的睾丸雌性化大鼠的研究，获得了关于雄激素依赖性和非依赖性控制脑芳香化酶的额外遗传证据。这些观察结果表明不同脑区存在酶反应性的关键差异。在几个核内，芳香化酶诱导的性别差异与核雄激素受体浓度的差异相关，表明对睾酮的神经反应性存在性别差异。雌二醇和双氢睾酮协同作用调节视前区的芳香化酶活性。此外，时间进程研究表明，雌激素处理增加了用双氢睾酮处理的雄性大鼠视前区核雄激素受体占据的持续时间。这些结果提示了雌激素和雄激素在细胞水平上相互作用以调节神经功能和行为的可能方式。
