Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression.
The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland.
Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin; Departments of Medicine, Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; hraff@mcw.edu.
Hershel
H
Raff
Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin;
Ashley
A
Gehrand
Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin;
Eric D
ED
Bruder
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
Matthew J
MJ
Hoffman
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota.
William C
WC
Engeland
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
Carol
C
Moreno
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D005260:Female; D055786:Gene Knockout Techniques; D005838:Genotype; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020303:Rats, Inbred Dahl; D055647:Rats, Transgenic; D012083:Renin / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects; D015383:Zona Fasciculata / Q000378:metabolism; D015384:Zona Glomerulosa / Q000378:metabolism; D015385:Zona Reticularis / Q000378:metabolism
D012333:RNA, Messenger; D000804:Angiotensin II; D000450:Aldosterone; D003994:Bucladesine; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D003345:Corticosterone
adrenal cortex; aldosterone; corticosterone; knockout rat; renin