Sierra A
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021, USA.
J Neuroendocrinol. 2004 Sep;16(9):787-93. doi: 10.1111/j.1365-2826.2004.01226.x.
The nervous system is a well-known target for steroid hormones, as these hormones regulate brain functions that include neuronal survival and differentiation, myelination, neurogenesis, plasticity and repair after injury. Furthermore, the brain is also a steroidogenic tissue because it possesses the enzymes required to metabolize the common precursor, cholesterol, into steroids, named 'neurosteroids'. The rate-limiting step in the synthesis of steroid hormones is the access of cholesterol, accumulated in the outer mitochondrial membrane, to the first steroidogenic enzyme, P450scc (cholesterol side-chain cleavage enzyme), located in the inner mitochondrial membrane. In the ovary and the adrenal gland, which comprise classic steroidogenic tissues, this process requires the steroidogenic acute regulatory protein (StAR) to facilitate the shuttle of cholesterol through the intermembrane space. The mechanism used by the brain to regulate the first stage of steroidogenesis remains unknown. Recently, several groups have investigated the potential presence of StAR in the nervous tissue and have concluded that StAR is widely expressed throughout the brain, although restricted to specific cell populations. New results concerning localization, regulation and possible functions of StAR in the brain are discussed.
神经系统是类固醇激素众所周知的作用靶点，因为这些激素调节大脑功能，包括神经元存活与分化、髓鞘形成、神经发生、可塑性以及损伤后的修复。此外，大脑也是一个类固醇生成组织，因为它拥有将常见前体胆固醇代谢为类固醇（称为“神经甾体”）所需的酶。类固醇激素合成中的限速步骤是积累在外线粒体膜中的胆固醇进入位于线粒体内膜的第一种类固醇生成酶P450scc（胆固醇侧链裂解酶）。在包括经典类固醇生成组织的卵巢和肾上腺中，这一过程需要类固醇生成急性调节蛋白（StAR）来促进胆固醇穿梭通过膜间隙。大脑调节类固醇生成第一阶段所使用的机制仍然未知。最近，几个研究小组调查了神经组织中StAR的潜在存在情况，并得出结论，StAR在整个大脑中广泛表达，尽管仅限于特定细胞群体。本文讨论了有关StAR在大脑中的定位、调节及其可能功能的新结果。
