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The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion

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Abstract

In order to evaluate the role of Src tyrosine kinase in thecal cell steroidogenesis, a pharmacological approach was utilized by treating enriched populations of mouse ovarian theca-interstitial cells in vitro with a direct Src kinase inhibitor, PP2. Inhibition of Src with PP2 increased both basal and forskolin-stimulated androstenedione secretion, and increased cytochrome P450 17-alpha hydroxylase-lyase (CYP17) promoter activity and steady state mRNA. PP2 did not change thecal levels of StAR mRNA. Inhibition of mitogen-activated protein kinase kinase, a downstream regulator of Src activity, using PD98059 also increased forskolin-stimulated secretion of androstenedione above forskolin alone, but had no effect on basal secretion of androstenedione. Src inhibition increased mitogen-activated protein kinase phosphatase-1 protein and decreased phosphorylation of SF-1, which correlated with increased CYP17 promoter activity and mRNA levels. These results implicate Src tyrosine kinase in the regulation of CYP17 and thecal androgen secretion.

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Acknowledgments

This work was supported by a U54 Center grant from the National Institute of Child Health and Human Development (HD 33994), which is a Specialized Cooperative Center Program in Reproduction Research (PFT), a grant from the National Center for Research Resources (RR-16475) to support a Kansas IDeA Network of Biomedical Research Excellence, and a KUMC Biomedical Research Training Fellowship (GC).

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, The Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Gaurav Chaturvedi, Koji Arai & Paul F. Terranova

  2. Department of Obstetrics and Gynecology, The Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Paul F. Terranova

  3. Department of Anatomy and Cell Biology, Center for Reproductive Sciences, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Katherine F. Roby

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  1. Gaurav Chaturvedi
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  2. Koji Arai
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Correspondence to Katherine F. Roby.

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Chaturvedi, G., Arai, K., Terranova, P.F. et al. The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion. Mol Cell Biochem 318, 191–200 (2008). https://doi.org/10.1007/s11010-008-9871-9

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  • DOI: https://doi.org/10.1007/s11010-008-9871-9

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