GLUCOCORTICOIDS AND ANABOLIC ANDROGENIC STEROIDS INHIBIT THE SYNTHESIS OF GABAERGIC STEROIDS IN RAT CORTEX/

Cerebral side effects of therapy with glucocorticoids include mental a lterations and behavioral disturbances such as nervousness, insomnia, changes in mood or psychological state and psychopathies of manic-depr essive or schizophrenic type. We have investigated the effects of gluc ocorticoids, anabolic/androgenic steroids and the 5-alpha-reductase in hibitor N,N-bis 3-oxo-4-aza-5-alpha-androstane-17-beta-carboxamide (1- MAC) on the synthesis of the GABAergic steroids 5-alpha-pregnane-3.20- dione (5-alpha-dihydroprogesterone) and 5-alpha-pregnane-3-alpha-ol-20 -one (5-alpha-tetrahydroprogesterone) in rat cortex in vitro. We found potent inhibition of progesterone-3-alpha-hydroxysteroid dehydrogenas e (3-alpha-HSDH) by prednisone, prednisolone, dexamethasone and fluoco rtolone. Inhibition of progesterone 5-alpha-reductase by glucocorticoi ds was not found. In addition, inhibition of 3-alpha-HSDH and 5-alpha- reductase by androgenic/anabolic steroids and inhibition of 5-alpha-re ductase by 1-MAC could be demonstrated. The inhibition of progesterone metabolism in the cerebral cortex by exogenous steroids might lead to altered neuronal activity. We conclude that this mechanism could indu ce the cerebral side effects, such as mental modifications and behavio ral disturbances, of the drugs investigated.