Lavaque E, Sierra A, Azcoitia I, Garcia-Segura L M
Instituto Cajal, CSIC, Madrid, Spain.
Neuroscience. 2006;138(3):741-7. doi: 10.1016/j.neuroscience.2005.05.060. Epub 2005 Dec 7.
The nervous system synthesizes steroids that regulate the development and function of neurons and glia, and have neuroprotective properties. The first step in steroidogenesis involves the delivery of free cholesterol to the inner mitochondrial membrane where it can be converted into pregnenolone by the enzyme cytochrome P450side chain cleavage. The peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein are involved in this process and appear to function in a coordinated manner. Steroidogenic acute regulatory protein mRNA and protein are widely expressed throughout the adult brain. Steroidogenic acute regulatory protein expression has been detected in many neuronal populations, in ependymocytes, in some astroglial cells, in Schwann cells from peripheral nerves and in proliferating cells of the developing and adult brain. Steroidogenic acute regulatory protein is colocalized in the same neural cells with P450side chain cleavage and with other steroidogenic enzymes. Steroidogenic acute regulatory protein expression in the brain shows marked changes with development, aging and injury. The steroidogenic acute regulatory protein gene may be under the control of diverse mechanisms in different neural cell types, since its expression is upregulated by cyclic AMP (cAMP) in gliomas and astrocytes in culture and downregulated by cyclic AMP (cAMP) in Schwann cells. In addition, activation of N-methyl-D-aspartate receptors, and the consequent rise in intracellular calcium levels, activates steroidogenic acute regulatory protein and steroidogenesis in hippocampal neurons. In conclusion, steroidogenic acute regulatory protein is regulated in the nervous system by different physiological and pathological conditions and may play an important role during brain development, aging and after injury.
神经系统合成的类固醇可调节神经元和神经胶质细胞的发育与功能，并具有神经保护特性。类固醇生成的第一步涉及将游离胆固醇转运至线粒体内膜，在那里它可被细胞色素P450侧链裂解酶转化为孕烯醇酮。外周型苯二氮䓬受体和类固醇生成急性调节蛋白参与此过程，且似乎以协调的方式发挥作用。类固醇生成急性调节蛋白的mRNA和蛋白在整个成人大脑中广泛表达。在许多神经元群体、室管膜细胞、一些星形胶质细胞、外周神经的雪旺细胞以及发育中和成人大脑的增殖细胞中均检测到类固醇生成急性调节蛋白的表达。类固醇生成急性调节蛋白与P450侧链裂解酶以及其他类固醇生成酶共定位于同一神经细胞中。大脑中类固醇生成急性调节蛋白的表达随发育、衰老和损伤而发生显著变化。类固醇生成急性调节蛋白基因在不同神经细胞类型中可能受多种机制的调控，因为其表达在培养的胶质瘤和星形胶质细胞中被环磷酸腺苷（cAMP）上调，而在雪旺细胞中被环磷酸腺苷（cAMP）下调。此外，N-甲基-D-天冬氨酸受体的激活以及随之而来的细胞内钙水平升高，可激活海马神经元中的类固醇生成急性调节蛋白和类固醇生成。总之，类固醇生成急性调节蛋白在神经系统中受不同生理和病理条件的调控，可能在大脑发育、衰老及损伤后发挥重要作用。
