Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse and rat Sertoli cells

Karel De Gendt, Evi Denolet, Ariane Willems, Veerle W Daniels, Liesbeth Clinckemalie, Sarah Denayer, Miles F Wilkinson, Frank Claessens, Johannes V Swinnen, Guido Verhoeven

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30 Citations (Scopus)

Abstract

Our previous analysis of Sertoli cell androgen receptor (AR) knockout (SCARKO) mice revealed that several cytoskeletal components are a potential target of androgen action. Here, we found that one of these components, the beta-tubulin isotype Tubb3, is differentially regulated in testes from SCARKO mice (relative to littermate controls) from Postnatal Day 10 to adulthood. The Tubb3 gene is unique in this respect, as at Day 10, no other beta-tubulin genes are significantly regulated by AR. We further characterized androgen regulation of Tubb3 in vivo and in vitro and demonstrated that it is a conserved feature in both mice and rats. To investigate whether androgens directly regulate Tubb3 expression, we screened for androgen response elements (AREs) in the Tubb3 gene. In silico analysis revealed the presence of four ARE motifs in Tubb3 intron 1, two of which bind to AR in vitro. Mutation of one of these (ARE1) strongly reduced androgen-dependent reporter gene expression. These results, coupled with the finding that the AR binds to the Tubb3 ARE region in vivo, suggest that Tubb3 is a direct target of AR. Our data strengthen the contention that androgens exert their effects on spermatogenesis, in part, through modulation of the Sertoli cell cytoskeleton. Androgen regulation of beta-tubulin has also been described in neurons, fortifying the already known similarity in microtubule organization in Sertoli cell processes and neurons, the only other cell type in which Tubb3 is known to be expressed.
Original languageEnglish
Pages (from-to)934-945
Number of pages12
JournalBiology of Reproduction
Volume85
Issue number5
DOIs
Publication statusPublished - 1 Nov 2011

Keywords

  • androgen receptor
  • androgens
  • cytoskeleton
  • fertility
  • microtubes
  • testis

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    De Gendt, K., Denolet, E., Willems, A., Daniels, V. W., Clinckemalie, L., Denayer, S., Wilkinson, M. F., Claessens, F., Swinnen, J. V., & Verhoeven, G. (2011). Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse and rat Sertoli cells. Biology of Reproduction, 85(5), 934-945. https://doi.org/10.1095/biolreprod.110.090704