Regulation of 5-hydroxytryptamine metabolism in mouse brain by adrenal glucocorticoids.

The effects of glucocorticoid hormone on the metabolism of brain 5-hydroxytryptamine (5-HT) were studied in mice. A single injection of hydrocortisone acetate (HCA; 20 mg/kg, i.p.) accelerated the accumulation of 5-HT in whole brain after inhibition of monoamine oxidase activity by paragyline. The hormone did not appear to change brain tryptophan hydroxylase or 5-hydroxytryptophan decarboxylase activity. However, tryptophan levels in brain were elevated by 50% within 1 h after treatment with HCA. The effect of HCA on brain tryptophan levels was localized mainly in the nerve endings. In vitro synaptosomal preparations, HCA at 10(-5)-10(-7)M or corticosterone at 10(-5) M was found to stimulate the uptake of L-[3H]-tryptophan by the synaptosomes while androgenic and progesterone-like steroids were ineffective. These results demonstrate that glucocorticoids may directly act on nerve terminals in the regulation of 5-HT synthesis through an action on the uptake of tryptophan.