Hutchison J B
MRC Neuroendocrine Development and Behaviour Group, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, England.
J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):509-20. doi: 10.1016/0960-0760(93)90255-u.
Estrogens are required for both the organization of the brain in early development and adult behavior. Two approaches have been used in our laboratory to study the behavioral role of brain aromatase. First, brain metabolism of testosterone (T) has been related to behavior in the same individual using a well established neuroendocrine model, the ring dove, in which estradiol-17 beta (E2) has specific effects on brain mechanisms of male behavior. Aromatase in preoptic area (POA) (a) has a high activity (Vmax) and strong substrate binding affinity (Km < 5 nM), (b) is regulated by both androgens and estrogens, and the type of regulation differs according to brain area, (c) is influenced by products of an endogenous inactivating pathway, 5 beta-reduction; 5 beta-dihydrotestosterone and other 5 beta-reduced metabolites appear to be non-genomic regulators of the brain aromatase. Preoptic aromatase activity is also influenced by photoperiod and socio-sexual stimuli. The codistribution of regulated aromatase activity and estrogen receptor cells is found to be T-dependent. Our second approach has been to relate the aromatase system to developmental sex differences in brain structure and behavior of the Mongolian gerbil. Neonatal gerbil aromatase is relatively active in the POA, but has a weaker T substrate-binding affinity (Km = 30 nM) than the dove. T acting via its metabolite, E2, masculinizes the sexually dimorphic area of the hypothalamus; the differentiating effect is asymmetric. We suggest that the regulation of the brain aromatase system may be lateralized during steroid-sensitive periods of development.
雌激素对于大脑在早期发育过程中的组织形成以及成年后的行为表现均是必需的。我们实验室采用了两种方法来研究脑芳香化酶的行为作用。首先，使用一种成熟的神经内分泌模型——环鸽，研究同一个体中睾酮（T）的脑代谢与行为之间的关系，其中雌二醇 - 17β（E2）对雄性行为的脑机制具有特定作用。视前区（POA）的芳香化酶：（a）具有高活性（Vmax）和强底物结合亲和力（Km < 5 nM）；（b）受雄激素和雌激素的双重调节，且调节类型因脑区而异；（c）受内源性失活途径产物5β - 还原作用的影响；5β - 二氢睾酮和其他5β - 还原代谢产物似乎是脑芳香化酶的非基因组调节剂。视前区芳香化酶活性还受光周期和社会性行为刺激的影响。发现受调节的芳香化酶活性与雌激素受体细胞的共分布是依赖于T的。我们的第二种方法是将芳香化酶系统与蒙古沙鼠大脑结构和行为的发育性性别差异联系起来。新生沙鼠的芳香化酶在视前区相对活跃，但与鸽子相比，其对T底物的结合亲和力较弱（Km = 30 nM）。T通过其代谢产物E2起作用，使下丘脑的性二态区男性化；这种分化作用是不对称的。我们认为，在发育的类固醇敏感时期，脑芳香化酶系统的调节可能存在偏侧化。
