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

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.