Aldosterone enhances renin gene expression in juxtaglomerular cells.
The secretion and synthesis of renin as the key regulator of the renin-angiotensin-aldosterone system are directly controlled by ANG II in the sense of a negative feedback. Because we found that renal afferent arterioles including the juxtaglomerular portion express the mineralocorticoid receptor, we aimed to characterize a possible direct effect of aldosterone on renin synthesis and renin secretion at the level of renal juxtaglomerular cells. Aldosterone (100 nM) clearly enhanced renin mRNA levels in primary cultures of mouse juxtaglomerular cells prestimulated with isoproterenol (100 nM) but had no effect on the exocytosis of stored renin. Similarly, in the mouse juxtaglomerular cell line As4.1, aldosterone time and concentration dependently increased renin mRNA abundance and prorenin secretion up to 2.5-fold. Moreover, aldosterone potentiated cAMP-induced renin gene expression in As4.1 cells. The effect of aldosterone was inhibited by spironolactone and was mimicked by corticosteroid hormones but not by sex steroids. Aldosterone had no influence on basal renin promoter activity but increased the renin mRNA half-life about threefold. In summary, these data suggest that aldosterone exerts a direct positive effect on renin gene expression at the cellular level probably by stabilizing renin mRNA.
Institut für Physiologie, Universität Regensburg, D-93040 Regensburg, Germany. juergen.klar@vkl.uni-regensburg.de
Jurgen
J
Klar
Helga
H
Vitzthum
Armin
A
Kurtz
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012083:Renin / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D000242:Cyclic AMP; D012083:Renin