Aldosterone biosynthesis in the rat brain.
Messenger RNA (mRNA) for enzymes involved in adrenal steroid biosynthesis are expressed in the brain, and the coded enzymes have been shown to be active. The expression of mRNA for the cytochrome P-450 enzyme aldosterone synthase, crucial for the final step in the synthesis of aldosterone and the synthesis of aldosterone was studied in several anatomic areas of the rat brain. Expression of the mRNA for the aldosterone synthase was demonstrated by RT-PCR/Southern blot in adrenal, aorta, hypothalamus, hippocampus, amygdala, cerebrum, and cerebellum. Incubation of brain minces from intact and adrenalectomized rats demonstrated the synthesis of corticosterone and aldosterone from endogenous precursors. Incubations of brain minces with [1,2(3)H]-deoxycorticosterone, followed by extraction and three different successive TLCs, demonstrated the presence of labeled aldosterone, corticosterone, and 18-hydroxy-deoxycorticosterone. Incubation, in the presence of 10 microM cortisol or metyrapone, inhibited the synthesis of aldosterone or both aldosterone and corticosterone, respectively. These studies indicate that the rat brain has the enzymatic machinery for the synthesis of adrenal corticosteroids and is capable of synthesizing aldosterone. Aldosterone synthesized in the brain might play a paracrine role in the regulation of blood pressure.
Gomez-Sanchez
C E
CE
Harry S. Truman Memorial Veterans Hospital, and Department of Internal Medicine, University of Missouri-Columbia, 65201, USA.
Zhou
M Y
MY
Cozza
E N
EN
Morita
H
H
Foecking
M F
MF
Gomez-Sanchez
E P
EP
D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D015139:Blotting, Southern; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D003900:Desoxycorticosterone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D003900:Desoxycorticosterone; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D003345:Corticosterone; D006854:Hydrocortisone; D008797:Metyrapone