Torres J M, Ruiz E, Ortega E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Spain.
Neurochem Res. 2001 May;26(5):555-8. doi: 10.1023/a:1010925331768.
The 3alpha-hydroxy ring A-reduced metabolite of progesterone, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) is among the most potent known ligands of the gamma aminobutyric acid (GABA) receptor, designated GABA-A, in the central nervous system. We determined by RIA serum levels of progesterone (PROG), 5-alpha-dihidroprogesterone (DHP) and allopregnanolone in male and female rats after corticotropin releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) administration. Allopregnanolone was undetectable in plasma and brain of control males but detectable in plasma and brain of males injected with CRH and ACTH and of control and similarly treated females. Allopregnanolone increased in the plasma and brain after CRH and ACTH administration in all cases. The data demonstrate that the administration of CRH plus ACTH results in a rapid increase of the neuroactive steroid allopregnanolone in the brain of males and females to levels known to modulate GABA-A receptor function. Thus, stress could regulate neurosteroid biosynthesis via the hormones ACTH and CRH.
孕酮的3α-羟基A环还原代谢产物，3α-羟基-5α-孕烷-20-酮（别孕烯醇酮）是中枢神经系统中已知的γ-氨基丁酸（GABA）受体（称为GABA-A）最有效的配体之一。我们通过放射免疫分析法测定了促肾上腺皮质激素释放激素（CRH）和促肾上腺皮质激素（ACTH）给药后雄性和雌性大鼠血清中孕酮（PROG）、5-α-二氢孕酮（DHP）和别孕烯醇酮的水平。对照组雄性大鼠的血浆和大脑中未检测到别孕烯醇酮，但在注射CRH和ACTH的雄性大鼠以及对照组和同样处理的雌性大鼠的血浆和大脑中可检测到。在所有情况下，CRH和ACTH给药后，血浆和大脑中的别孕烯醇酮均增加。数据表明，CRH加ACTH给药导致雄性和雌性大鼠大脑中神经活性类固醇别孕烯醇酮迅速增加至已知可调节GABA-A受体功能的水平。因此，应激可能通过ACTH和CRH激素调节神经甾体生物合成。
