Effects of CRH and ACTH administration on plasma and brain neurosteroid levels

The 3 alpha -hydroxy ring A-reduced metabolite of progesterone, 3 alpha -hy droxy-5 alpha -pregnan-20-one (allopregnanolone) is among the most potent k nown ligands of the gamma aminobutyric acid (GABA) receptor, designated GAB A-A, in the central nervous system. We determined by RIA serum levels of pr ogesterone (PROG), 5-alpha -dihidroprogesterone (DHP) and allopregnanolone in male and female rats after corticotropin releasing hormone (CRH) and adr enocorticotropin hormone (ACTH) administration. Allopregnanolone was undete ctable in plasma and brain of control males but detectable in plasma and br ain of males injected with CRH and ACTH and of control and similarly treate d females. Allopregnanolone increased in the plasma and brain after CRH and ACTH administration in all cases. The data demonstrate that the administra tion of CRH plus ACTH results in a rapid increase of the neuroactive steroi d allopregnanolone in the brain of males and females to levels known to mod ulate GABA-A receptor function. Thus, stress could regulate neurosteroid bi osynthesis via the hormones ACTH and CRH.