title: Renin and prorenin have no direct effect on aldosterone synthesis in the human adrenocortical cell lines H295R and HAC15.
abstract: BACKGROUND
  Transgenic rats expressing the human (pro)renin receptor (h(P)RR) have elevated plasma aldosterone levels despite unaltered levels, in plasma and adrenal, of renin and angiotensin II.
  
  
  METHODS
  To investigate whether renin/prorenin-(P)RR interaction underlies these elevated aldosterone levels, the effect of (pro)renin on steroidogenesis was compared with that of angiotensin II in two (P)RR-expressing human adrenocortical cell lines, H295R and HAC15. Angiotensin II rapidly induced extracellular signal-regulated kinase (ERK) phosphorylation and increased the expression of STAR, CYP21A2, CYP11B2, and CYP17A1 at 6 and 24 hours, whereas the expression of CYP11A1 and HSD3B2 remained unaltered. Incubation with renin or prorenin at nanomolar concentrations had no effect on the expression of any of the steroidogenic enzymes tested, nor resulted in ERK phosphorylation. Angiotensin II, but not renin or prorenin, induced aldosterone production.
  
  
  CONCLUSIONS
  Although the (P)RR is present in adrenocortical cells, renin and prorenin do not elicit ERK phosphorylation nor directly affect steroid production via this receptor at nanomolar concentrations. Thus, direct (pro)renin-(P)RR interaction is unlikely to contribute to the elevated aldosterone levels in human (P)RR transgenic rats. This conclusion also implies that the aldosterone rise that often occurs during prolonged renin-angiotensin system blockade is rather due to the angiotensin II 'escape' during such blockade.
authors.affiliation: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Centre Rotterdam, The Netherlands.
authors.forename: Pieter M
authors.initials: PM
authors.lastname: Jansen
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofland
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D012083:Renin / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D000450:Aldosterone; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor