CORTICOSTEROID SYNTHESIS IN THE CENTRAL-NERVOUS-SYSTEM

The possibility that adrenocorticosteroids might be synthesized in the central nervous system was assessed by RT-PCR using primers for the C YP11B1 gene which codes for 11 beta-hydroxylase, the enzyme responsibl e for corticosterone and cortisol formation in the zona fasciculata, i ncubation of minces of several areas of the brain with H-3-DOC and mea suring steroid metabolites, and determining the effect of the intracer ebroventricular infusion of the 11 beta-hydroxylase mechanism-based in hibitor 19-ethynyldeoxycorticosterone upon the salt-induced increase i n blood pressure in SS/jr rats. Significant, though small relative to the adrenal, amounts of mRNA for 11 beta-hydroxylase was found in the aorta, cerebrum, cerebellum, hippocampus, hypothalamus and amygdala, b ut not in the heart. Brain minces converted H-3-DOC to corticosterone and 11-dehydrocorticosterone to a greater degree than to 18-OH-DOG. Th e effect of 19-ethynyIdeoxycorticosterone was dose dependent, with the lower doses preventing salt-induced hypertension and the higher doses having no effect or increasing the blood pressure.