Glucocorticoids as a regulatory factor for brain tryptophan hydroxylase during development.

Chronic administration of corticosterone (5 mg/kg) to developing rats induced an increase of tryptophan hydroxylase (TPH) activity in midbrain, but the responsivity of the enzyme to the steroid appeared to be limited only to a brief neonatal period (days 6-12). Reserpine (5 mg/kg) induced an increase of midbrain TPH activity also only after 5 days of postnatal life, but the responsivity of the enzyme to reserpine continued after day 12 and throughout adulthood. Thus, the effect of the glucocorticoid and that of reserpine on TPH may involve different mechanisms. Although corticosterone showed no apparent "inductive" effect after day 12, developmental rise of midbrain TPH activity after day 12 was found to be totally abolished by bilateral adrenalectomy. Replacement with corticosterone to the adrenalectomized rats restored normal enzyme development. It appears that glucocorticoids are involved in a "permissive" role in the developmental rise of TPH activity in midbrain.