gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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Expression of the alpha-subunit of the epithelial sodium channel (alpha-ENAC) is stimulated by testosterone in the human renal cell line HKC-8

Die alpha-Untereinheit des epithelialen Natriumkanals wird durch Testosteron in der menschlichen Nierenzelllinie HKC-8 stimuliert

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  • M.O. Quinkler - Charité Campus Mitte Berlin (Berlin, D)
  • I.J. Bujalska - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • K. Kaur - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • C.U. Onyimba - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • P.M. Stewart - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP9

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch009.shtml

Published: August 8, 2006

© 2006 Quinkler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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In human studies there is no difference in blood pressure between boys and girls, but following puberty, blood pressure increases more in men than in women suggesting sex-specific differences in blood pressure regulation. Modulation of epithelial sodium reabsorption through the expression and activity of ENaC is an important component in the control of sodium balance. We investigated the androgen-dependent regulation of alpha-ENaC using the human renal cell line HKC-8 as a model.

We investigated the androgen-dependent regulation of alpha-ENaC in human kidney and a human renal cell line HKC-8. Androgen receptor (AR) expression was studied on mRNA and protein levels. We used Affymetrix microarray techniques to analyse androgen-dependent gene regulation in HKC-8 cells and performed Taq Man quantitative RT-PCR for verification. HKC-8 cells were transfected with different human alpha-ENaC promoter-reporter constructs and regulation by testosterone was studied.

AR was expressed in male kidney and HKC-8 cells at both the mRNA and protein level. The Affymetrix assay showed a significant increase in alpha-ENaC mRNA expression by testosterone. Taq Man PCR revealed the highest alpha-ENaC induction with 50nM testosterone at 48h. The induction by testosterone was completely blocked by adding the AR antagonist flutamide. Transcription factor database analysis of the alpha-ENaC promoter sequence identified a putative AR response element (ARE) located 140 nucleotides upstream from the transcription start-site of exon 1A. HKC-8 cell transfection studies showed that testosterone directly up-regulated gene expression via this ARE.

These data show that alpha-ENaC expression is regulated directly by testosterone and highlight a potential mechanism explaining the reported gender differences in blood pressure.