cGMP-dependent protein kinase type II regulates basal level of aldosterone production by zona glomerulosa cells without increasing expression of the steroidogenic acute regulatory protein gene.
The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of salt and water homeostasis. Here, we demonstrate the expression and functional role of cGMP-dependent protein kinases (PKGs) in rat adrenal cortex. Expression of PKG II is restricted to adrenal zona glomerulosa (ZG) cells, whereas PKG I is localized to the adrenal capsule and blood vessels. Activation of the aldosterone system by a low sodium diet up-regulated the expression of PKG II, however, it did not change PKG I expression in adrenal cortex. Both, activation of PKG II in isolated ZG cell and adenoviral gene transfer of wild type PKG II into ZG cells enhanced aldosterone production. In contrast, inhibition of PKG II as well as infection with a PKG II catalytically inactive mutant had an inhibitory effect on aldosterone production. Steroidogenic acute regulatory (StAR) protein that regulates the rate-limiting step in steroidogenesis is a new substrate for PKG II and can be phosphorylated by PKG II in vitro at serine 55/56 and serine 99. Stimulation of aldosterone production by PKG II in contrast to stimulation by PKA did not activate StAR gene expression in ZG cells. The results presented indicate that PKG II activity in ZG cells is important for maintaining basal aldosterone production.
Gambaryan
Stepan
S
Institute of Clinical Biochemistry and Pathobiochemistry Medical University Clinic Wuerzburg, Josef Schneider Strasse 2, 97080 Wuerzburg, Germany. gambarya@klin-biochem.uni-wuerzburg.de
Butt
Elke
E
Marcus
Katrin
K
Glazova
Margarita
M
Palmetshofer
Alois
A
Guillon
Gilles
G
Smolenski
Albert
A
D000256:Adenoviridae / Q000235:genetics; D000302:Adrenal Cortex / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002384:Catalysis; D017364:Collagenases / Q000378:metabolism; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D009154:Mutation; D010750:Phosphoproteins / Q000096:biosynthesis*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation; D015384:Zona Glomerulosa / Q000166:cytology* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D018076:DNA, Complementary; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D000098682:Steroidogenic Acute Regulatory Protein; D000450:Aldosterone; D012964:Sodium; D005982:Glutathione Transferase; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; C569732:Prkg2 protein, rat; D017364:Collagenases