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J. Biol. Chem., Vol. 278, Issue 32, 29640-29648, August 8, 2003

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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^*

Stepan Gambaryan  , Elke Butt , Katrin Marcus ¶ ||, Margarita Glazova  **, Alois Palmetshofer , Gilles Guillon  and Albert Smolenski ¶ ||

From the Institute of Clinical Biochemistry and Pathobiochemistry Medical University Clinic Wuerzburg, Josef Schneider Strasse 2, 97080 Wuerzburg, Germany, the ^**Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia, INSERM U 469, 141, 34094 Montpellier, cedex 05, France, the ^¶Medical Proteome Center, 44780 Bochum, Germany, and the ^||Institute of Biochemistry II Medical University Clinic Frankfurt, 60590 Frankfurt, Germany

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.

Received for publication, February 28, 2003 , and in revised form, May 23, 2003.

^* This work was supported by the Deutsche Forschungsgemeinschaft Grants WA366, Bu740, and SFB355. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 49-931-201-45154; Fax: 49-931-201-45137; E-mail: gambarya{at}klin-biochem.uniwuerzburg.de.

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