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.
D006916:5-Hydroxytryptophan; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D004296:Dopa Decarboxylase / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D013268:Stimulation, Chemical; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D012701:Serotonin; D014443:Tyrosine; D014364:Tryptophan; D010293:Pargyline; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase; D004296:Dopa Decarboxylase; D003345:Corticosterone; D006854:Hydrocortisone