Section of Obstetrics and Gynecology, Department of Clinical Science, Umeå Neurosteroid Research Center, Umeå University Umeå, Sweden.
Front Endocrinol (Lausanne). 2011 Oct 4;2:44. doi: 10.3389/fendo.2011.00044. eCollection 2011.
Neurosteroids represent a class of endogenous steroids that are synthesized in the brain, the adrenals, and the gonads and have potent and selective effects on the GABAA-receptor. 3α-hydroxy A-ring reduced metabolites of progesterone, deoxycorticosterone, and testosterone are positive modulators of GABA(A)-receptor in a non-genomic manner. Allopregnanolone (3α-OH-5α-pregnan-20-one), 5α-androstane-3α, 17α-diol (Adiol), and 3α5α-tetrahydrodeoxycorticosterone (3α5α-THDOC) enhance the GABA-mediated Cl(-) currents acting on a site (or sites) distinct from the GABA, benzodiazepine, barbiturate, and picrotoxin binding sites. 3α5α-P and 3α5α-THDOC potentiate synaptic GABA(A)-receptor function and activate δ-subunit containing extrasynaptic receptors that mediate tonic currents. On the contrary, 3β-OH pregnane steroids and pregnenolone sulfate (PS) are GABA(A)-receptor antagonists and induce activation-dependent inhibition of the receptor. The activities of neurosteroid are dependent on brain regions and types of neurons. In addition to the slow genomic action of the parent steroids, the non-genomic, and rapid actions of neurosteroids play a significant role in the GABA(A)-receptor function and shift in mood and memory function. This review describes molecular mechanisms underlying neurosteroid action on the GABA(A)-receptor, mood changes, and cognitive functions.
神经甾体代表了一类内源性甾体，它们在大脑、肾上腺和性腺中合成，并对 GABAA 受体具有强大而选择性的作用。孕酮、脱氧皮质酮和睾酮的 3α-羟基 A 环还原代谢物以非基因组方式作为 GABA(A)-受体的正调节剂。别孕烯醇酮（3α-OH-5α-孕烷-20-酮）、5α-雄烷-3α,17α-二醇（Adiol）和 3α5α-四氢脱氧皮质酮（3α5α-THDOC）增强 GABA 介导的 Cl(-)电流，作用于不同于 GABA、苯二氮䓬、巴比妥和苦毒蕈碱结合位点的位点（或位点）。3α5α-P 和 3α5α-THDOC 增强突触 GABA(A)-受体功能，并激活含有 δ 亚基的 extrasynaptic 受体，介导紧张性电流。相反，3β-OH 孕烷甾体和孕烯醇酮硫酸盐（PS）是 GABA(A)-受体拮抗剂，并诱导受体的激活依赖性抑制。神经甾体的活性取决于脑区和神经元类型。除了母体甾体的缓慢基因组作用外，神经甾体的非基因组和快速作用在 GABA(A)-受体功能和情绪及记忆功能的转变中发挥着重要作用。本综述描述了神经甾体对 GABA(A)-受体、情绪变化和认知功能的作用的分子机制。
