Professor of Physiology
Dr. Náray-Fejes-Tóth received her M.D. from the Semmelweis University Medical School in Budapest, Hungary in 1972. From 1974 to 1981 she was an Assistant Professor and later an Associate Professor of Biochemistry at the Semmelweis University Medical School. Then she worked for three years in Germany and spent a year in 1982 as a visiting scientist at Dartmouth. From 1985 to 1990 she worked at the Henry Ford Hospital in Detroit. She joined the Physiology Department at Dartmouth as an Associate Professor in 1990, and was promoted to Professor of Physiology in 1995.
The major research interest of Dr. Náray-Fejes-Tóth is the cellular and molecular mechanisms by which steroid hormones regulate kidney function and blood pressure. One project in her laboratory focuses on the elucidation of mechanisms that confer aldosterone-selectivity to mineralocorticoid target tissues. This study is based on the observation that the mineralocorticoid receptor apparently cannot distinguish between aldosterone and endogenous glucocorticoids, the blood levels of which are ~1000-fold higher than those of aldosterone. Aldosterone-selectivity in target cells is conferred by an enzyme, 11ß-hydroxysteroid dehydrogenase, which metabolizes glucocorticoids to a biologically inactive form, and thereby allows aldosterone to occupy its receptor. Dr. Náray-Fejes-Tóth's laboratory discovered a new form of this enzyme, which is specifically present in aldosterone-target cells. The laboratory cloned the cDNA of this novel enzyme and currently examines its intracellular localization and the regulation of its cell-specific expression. Recent studies proved that mutations in the gene of this enzyme causes a fatal disase in children, called apparent mineralocorticoid excess.
Another project deals with the identification of early-induced genes regulated by corticosteroid hormones. Although the regulatory effect of aldosterone on sodium homeostasis and thereby blood pressure has been known for decades, the exact molecular steps through which these effects are achieved are still unclear. The goal of this project is to identify and characterize those genes that mediate the biological effect of aldosterone on sodium transport. Both projects involve molecular biological techniques and functional studies.
Náray-Fejes-Tóth, A. and G. Fejes-Tóth Extranuclear localization of endogenous 11ß-hydroxysteroid dehydrogenase-2 in aldosterone target cells. Endocrinology, 139, 2955- 2958, 1998.
Fejes-Tóth, G., D. Pearce, and Náray-Fejes-Tóth. Subcellular localization of mineralocorticoid receptors in living cells: Effects of agonists and antagonists. Proc. Natl. Acad. Sci. USA, 95:2973-2978, 1998.
Náray-Fejes-Tóth, I. C. Colombowala, and G. Fejes-Tóth. The role of 11ß-hydroxysteroid dehydrogenase in steroid hormone specificity. J. Steroid Biochem. Molec. Biol., 65:311-316 1998.
Náray-Fejes-Tóth, A., C. Canessa, E.S. Cleaveland, G. Aldrich and G. Fejes-Tóth. Sgk is an aldosterone-induced kinase in the renal collecting duct: effects on epithelial Na channels. J. Biol. Chem, 274: 16973-16978, 1999.
Alvarez de la Rosa, D., P. Zhang, A. Náray-Fejes-Tóth, G. Fejes-Tóth and C. M. Canessa. The serum- and glucocorticoid-induced kinase sgk increases the abundance of epithelial Na channels in the plasma membrane of Xenopus oocytes. J. Biol. Chem. 274: 37834-9, 1999.
Náray-Fejes-Tóth, A., and G. Fejes-Tóth. Sgk, an aldosterone-induced early-response gene in mineralocorticoid target cells, regulates epithelial sodium channel. Kidney Int., 57:1290-1294, 2000.
Náray-Fejes-Tóth, A., G. Fejes-Tóth, K.A. Volk and J.B. Stokes. SGK is a primary glucocorticoid-induced gene in human. J. Steroid Biochem. Mol. Biol. 75:51-56, 2000
Pearce D, Náray-Fejes-Toth A, and Fejes-Toth G. Determinants of subnuclear organization of mineralocorticoid receptor characterized through analysis wild type and mutant receptors. J Biol Chem. 277:1451-6. 2002.
Helms,M.N., G. Fejes-Tóth and A. Náray-Fejes-Tóth. Hormone-regulated transepithelial Na transport in mammalian CCD cells requires SGK1 expression. Am. J. Physiol, Renal,284:F480-F487, 2003.Náray-Fejes-Tóth, A., M. N. Helms, J. B. Stokes and G. Fejes-Tóth. Regulation of sodium transport in mammalian collecting duct cells by aldosterone-induced kinase, SGK1: Structure/function studies. Mol. Cell. Endocrin. 217:197-202, 2004.
Náray-Fejes-Tóth, A, and Fejes-Tóth, G. The Kidney-Specific WNK1 Isoform Is Induced By Aldosterone And Stimulates ENaC-Mediated Na+ Transport. Proc. Natl. Acad. Sci. USA, 101:17434-9, 2004.Boyd, C. and Náray-Fejes-Tóth, A. Gene Regulation of ENaC subunits by Serum and Glucocorticoid Inducible Kinase-1 (SGK1). Am. J. Pysiol: Renal. 288: F505-F512, 2005.
Náray-Fejes-Tóth, A. and Fejes-Tóth, G. Generation and characterization of a mouse strain with selective expression of Cre recombinase in 11ß-hydroxysteroid dehydrogenase 2 expressing cells. Am. J. Physiol,: Renal; 292, F486-94. 2007, Epub 2006 Aug 8
Fejes-Tóth, G. and Náray-Fejes-Tóth, A. Early Aldosterone-Regulated Genes in Cardiomyocytes: Clues to Cardiac Remodeling? Endocrinology, 147:1343-1348, 2007; e-published. Jan 18 2007
Cordas, E.A., Náray-Fejes-Tóth, and Fejes-Tóth G. Subcellular localization of the serum- and glucocorticoid-induced kinase (SGK1) in epithelial cells. Am. J. Physiol: Cell; 292:C1971-81, 2007. Epub Jan 3. 2007Martel, JA, Michael, D, Fejes-Tóth, G. and Náray-Fejes-Tóth, A. Melanophilin, a Novel Aldosterone-Induced Gene in Mouse Cortical Collecting Duct Cells. Am. J. Physiol,: 2007 Jul 3; [Epub ahead of print].
Boyd, C. and Náray-Fejes-Tóth, A. Steroid-mediated Regulation of the Epithelial Sodium Channel Subunits in Mammary Epithelial Cells. Endocrinology,;148, 3958-67, 2007. Epub 2007 May 17.
[8/22/07]