Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

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Class I PI3Ks are important signalling enzymes and drug targets in cancer and inflammation. We report that p110α and p110β, the two ubiquitously expressed class I PI3K isoforms, control fertility, with no evidence for such a role for p110δ, a PI3K highly expressed in leukocytes. Infertility is therefore a possible but reversible side-effect of PI3K-targeted therapies. Using a new mouse model of systemic p110β inactivation, we found that p110β is critical for ensuring the quality of eggs in females and for sperm formation in males. p110β inactivation leads to a specific blockade in sperm development, without affecting the spermatogenic stem cell pool. This, together with the observation that p110β inactivation has no detectable organismal side effects in the adult stage, makes this kinase a potential drug target for a male contraceptive. Besides its previously reported role in the spermatogenic cells themselves, we now report that p110β also regulates the action of androgens, the male sex hormones, specifically in the Sertoli cells that surround the developing sperm, without affecting androgen action in other tissues. In cancer, however, p110β may acquire the capacity to regulate androgen action in tissues other than Sertoli cells, as was previously documented in prostate cancer.

Vyšlo v časopise: Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005304
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005304

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