Steroidogenic Enzyme Gene Expression in the Human Heart 1

Abstract

Corticosteroids have specific effects on cardiac structure and function mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors. Aldosterone and corticosterone are synthesized in the rat heart. To see whether they might also be synthesized in the human cardiovascular system, we examined the expression of genes for steroidogenic enzymes as well as genes for GR, MR, and 11-hydroxysteroid dehydrogenase (11-HSD2; which maintains the specificity of MR). Human samples were from left and right atria, left and right ventricles, aorta, apex, intraventricular septum, and atrioventricular node as well as whole adult and fetal heart. Using RT-PCR, messenger ribonucleic acids encoding cholesterol side-chain cleavage enzyme (CYP11A), 3beta-HSD2, 21-hydroxylase (CYP21), 11beta-hydroxylase (CYP11B1), GR, MR, and 11-HSD2 were detected in all samples with the exception of the ventricles, which did not express CYP11B1. Aldosterone synthase (CYP11B2) messenger ribonucleic acid was detected in the aorta and fetal heart, but not in any region of the adult heart, and 17alpha-hydroxylase (CYP17) was not detected in any cardiac sample. Levels of steroidogenic enzyme gene expression were typically 0.1% those in the adrenal gland. These findings are consistent with autocrine or paracrine roles for corticosterone and deoxycorticosterone, but not cortisol or aldosterone, in the normal adult human heart.