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International Journal of Hypertension
Volume 2012, Article ID 724240, 7 pages
http://dx.doi.org/10.1155/2012/724240
Research Article

From Rat to Human: Regulation of Renin-Angiotensin System Genes by Sry

1Department of Biology and Integrated Bioscience Ph.D. Program, The University of Akron, Akron, OH 44325-3908, USA
2Nephrology Division, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, SP, Brazil
3Division of Mathematics and Sciences, Walsh University, North Canton, OH 44720, USA
4Department of Physiology and Biophysics, ICB, Federal University of Minas Gerais, 31270-010 Belo Horizonte, MG, Brazil

Received 29 July 2011; Revised 27 September 2011; Accepted 28 September 2011

Academic Editor: Anderson J. Ferreira

Copyright © 2012 Jeremy W. Prokop et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The testis determining protein, Sry, has functions outside of testis determination. Multiple Sry loci are found on the Y-chromosome. Proteins from these loci have differential activity on promoters of renin-angiotensin system genes, possibly contributing to elevation of blood pressure. Variation at amino acid 76 accounts for the majority of differential effects by rat proteins Sry1 and Sry3. Human SRY regulated rat promoters in the same manner as rat Sry, elevating Agt, Ren, and Ace promoter activity while downregulating Ace 2. Human SRY significantly regulated human promoters of AGT, REN, ACE2, AT2, and MAS compared to control levels, elevating AGT and REN promoter activity while decreasing ACE2, AT2, and MAS. While the effect of human SRY on individual genes is often modest, we show that many different genes participating in the renin-angiotensin system can be affected by SRY, apparently in coordinated fashion, to produce more Ang II and less Ang-(1–7).