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 CYP11B1 gene which codes for 11 beta-hydroxylase, the enzyme responsible for corticosterone and cortisol formation in the zona fasciculata, incubation of minces of several areas of the brain with 3H-DOC and measuring steroid metabolites, and determining the effect of the intracerebroventricular infusion of the 11 beta-hydroxylase mechanism-based inhibitor 19-ethynyldeoxycorticosterone upon the salt-induced increase in 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, but not in the heart. Brain minces converted 3H-DOC to corticosterone and 11-dehydrocorticosterone to a greater degree than to 18-OH-DOC. The effect of 19-ethynyldeoxycorticosterone was dose dependent, with the lower doses preventing salt-induced hypertension and the higher doses having no effect or increasing the blood pressure.
Gomez-Sanchez
C E
CE
Department of Internal Medicine, Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.
Zhou
M Y
MY
Cozza
E N
EN
Morita
H
H
Eddleman
F C
FC
Gomez-Sanchez
E P
EP
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000679:Amygdala / Q000201:enzymology; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000201:enzymology; D003345:Corticosterone / Q000096:biosynthesis; D003900:Desoxycorticosterone / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology; D006854:Hydrocortisone / Q000096:biosynthesis; D007031:Hypothalamus / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000235:genetics; D014316:Tritium
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D014316:Tritium; D003900:Desoxycorticosterone; D013252:Steroid 11-beta-Hydroxylase; D012194:RNA-Directed DNA Polymerase; D003345:Corticosterone; D006854:Hydrocortisone