Horm Metab Res 2009; 41(5): 356-362
DOI: 10.1055/s-0029-1192033
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Sex-specific Regulation of ENaC and Androgen Receptor in Female Rat Kidney

T. Kienitz 1 , B. Allolio 2 , C. J. Strasburger 1 , M. Quinkler 1
  • 1Clinical Endocrinology, Department of Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany
  • 2Department of Endocrinology, Medical University Würzburg, Würzburg, Germany
Further Information

Publication History

received 05.10.2008

accepted 07.01.2009

Publication Date:
17 February 2009 (eFirst)

Abstract

With the beginning of puberty blood pressure increases and is persistently higher in men than in premenopausal women. Sex steroids are known to have complex effects on the renal and cardiovascular system and are involved in blood pressure regulation. The epithelial sodium channel (ENaC) modulates sodium reabsorption in the kidney, but little is known about sex-specific regulation of ENaC subunit expression. Regulation of the androgen receptor (AR) is known to be tissue-specific and age-dependent, but not well studied in the kidney. We investigated the effects of sex steroids on ENaC subunits and renal AR expression in an in vivo rat model. Ovariectomized female Wistar rats were treated with placebo, testosterone, 5 α-dihydrotestosterone (DHT) or 17 β-estradiol (E2) for 14 days, and quantitative PCR and Western immunoblots were performed. DHT significantly decreased expression of all ENaC subunits in female rats, whereas testosterone showed only a trend to lower ENaC expression. These results are in contrast to previous studies where stimulating effects of androgens on the alpha-subunit of ENaC were seen. AR mRNA expression showed a trend to lower levels in females after testosterone treatment in this study. However, estrogen treatment significantly downregulated AR mRNA expression. In male control animals we were able to show a significantly increased expression of AR mRNA upon testosterone treatment. Our data demonstrate that AR and ENaC are regulated by sex steroids. That way sex steroids might modulate renal sodium reabsorption and therefore provide a possible explanation for sex differences in blood pressure.

References

Correspondence

M. Quinkler, MD 

Clinical Endocrinology

Department of Internal Medicine, Gastroenterology, Hepatology and Endocrinology Charité Campus Mitte

Charité Universitätsmedizin Berlin

Charitéplatz 1

10117 Berlin

Germany

Phone: +49/30/4505 142 59

Fax: +49/30/4505 149 58

Email: marcus.quinkler@charite.de