Purdy R H, Morrow A L, Moore P H, Paul S M
Department of Organic Chemistry, Southwest Foundation for Biomedical Research, San Antonio, TX 78228.
Proc Natl Acad Sci U S A. 1991 May 15;88(10):4553-7. doi: 10.1073/pnas.88.10.4553.
A 3 alpha-hydroxy A-ring-reduced metabolite of progesterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3 alpha,21-dihydroxy-5 alpha-pregnan-20- one (allotetrahydroDOC), are among the most potent known ligands of gamma-aminobutyric acid (GABA) receptors designated GABAA in the central nervous system. With specific radioimmunoassays, rapid (less than 5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swin stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (greater than 3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function.
孕酮的一种3α-羟基A环还原代谢产物，3α-羟基-5α-孕烷-20-酮（别孕烯醇酮），以及脱氧皮质酮（DOC）的一种代谢产物，3α,21-二羟基-5α-孕烷-20-酮（别四氢脱氧皮质酮），是中枢神经系统中已知的γ-氨基丁酸（GABA）受体GABAA最有效的配体之一。通过特异性放射免疫测定法，在暴露于环境温度游泳应激后的大鼠大脑（大脑皮层和下丘脑）和血浆中，检测到别孕烯醇酮和别四氢脱氧皮质酮迅速（少于5分钟）且显著（4至20倍）增加。在游泳应激前后，肾上腺切除大鼠的血浆中均未检测到这两种类固醇。然而，肾上腺切除后，大脑皮层中仍存在别孕烯醇酮（大于3 ng/g），但别四氢脱氧皮质酮不存在。这些数据证明大脑中存在别孕烯醇酮和别四氢脱氧皮质酮，并表明急性应激会导致这些神经活性类固醇迅速增加至已知可调节GABAA受体功能的水平。
