Colocalization of 11 beta-hydroxysteroid dehydrogenase and mineralocorticoid receptors in cultured vascular smooth muscle cells.
Colocalization of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid dehydrogenase (11-HSD), the enzyme acting as a protector of MR, in the same cell of mineralocorticoid (MC)-responsive tissues is crucial to the concept of enzymic regulation of intracellular cortisol levels in these tissues. Such colocalization was demonstrated in the epithelial cells of the renal distal tubule. The aim of the present study was to examine if MR and 11-HSD activity can be colocalized in cells of another target tissue to mineralocorticoids, the arteries. Vascular smooth muscle (VSM) cells were cultured, and absence of dedifferentiation was ascertained up to the eighth passage. High affinity binding of [3H]aldosterone (ALDO) was demonstrated in the intact cultured cells, and Kd and Bmax values were calculated from Scatchard plots. The activity of 11-HSD was demonstrated in the cultured cells by incubating them with [3H]-cortisol in the presence of cofactors, and isolating [3H]-cortisone. Other [3H]-metabolites formed were 11 beta-hydroxy- and 11-keto-androstenedione. These data support the view that arterial tree is a target organ for mineralocorticoids and may be of importance in the pathogenetic mechanism of MC-induced hypertension.
Kornel
L
L
Steroid Research Laboratory, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000493:pharmacokinetics; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D011817:Rabbits; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone