Estrogen Synthesis in Brain and its Functional Role

类固醇激素在脊椎动物的整个生命周期和发育过程中对中枢神经系统的结构和功能产生了深远的影响。虽然睾丸激素和雌二醇的主要来源来自性腺，但大脑也会产生类固醇。负责将雄激素代谢成雌激素的芳香酶定位于大脑不同区域的特定靶神经元中，如下丘脑。在一些脊椎动物中，在睾丸或肾上腺中没有发现芳香酶。施林格博士将确定这些男性体内循环雌激素的主要来源是否来自大脑中雄激素的芳构化。这具有重要的理论意义，因为大脑不仅可能是类固醇激素的靶子，也可能是循环中类固醇的主要来源。他还将研究大脑雌激素合成在大脑发育和功能性别差异调节中的作用。为了实现这些目标，施林格博士将测量注射雄激素后，不同脑区、非神经组织和血管系统中恢复的雌激素量。然后，他将确定大脑产生雌激素的雄激素底物的来源。最后，施林格博士将量化芳香酶的活性，并确定它们在下丘脑神经元中的亚细胞定位。这些研究将导致对荷尔蒙-大脑相互作用机制的新见解。增加我们对正常神经内分泌事件的基本过程的了解，将有助于更好地了解因接触特定类固醇激素不足和/或过多而导致的出生缺陷。

Steroid hormones profoundly influence the structure and function of the central nervous system during development and throughout the vertebrates' lifespan. While the major source of testosterone and estradiol comes from the gonads, the brain also produces steroids. Aromatase enzymes responsible for the metabolism of androgen into estrogen are localized within specific target neurons in discrete brain regions, such as the hypothalamus. In some species of vertebrates, aromatase is not found in testes or adrenals. Dr. Schlinger will determine whether the major source of circulating estrogen in these males is derived from aromatization of androgens in the brain. This has important theoretical ramifications because the brain may not only be a target of steroid hormones but also a major source of a circulating steroid. He will also examine the role of brain estrogen synthesis in the regulations of sex differences in brain development and function. To accomplish these goals, Dr. Schlinger will measure the amount of estrogen recovered in discrete brain regions, non-neural tissues and the vascular system following injection of androgen. He will then identify the source of the androgen substrate for the brain to produce estrogen. Finally, Dr. Schlinger will quantify the activity of aromatase enzymes and define their subcellular localization within neurons of the hypothalamus. These studies will lead to new insights in the mechanisms underlying hormone-brain interactions. Increasing our knowledge about the basic processes underlying normal neuroendocrine events will contribute towards to a better understanding of birth defects that result from insufficient and/or excessive exposure to a particular steroid hormone.