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Endocrine Mechanisms, Androgen Receptor and Carcinogenesis, and Hormone Escape

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Prostate Cancer: A Comprehensive Perspective

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Abstract

Androgens play important roles during the development and maintenance of normal prostate as well as during the progression of prostate cancer. Testosterone, which is synthesized in the testes under the control of hormones from the pituitary and hypothalamus, is the primary androgen in men. Testosterone enters the prostate through blood stream and binds its cognate receptor (the androgen receptor or AR) in the acinar epithelial cells and the stromal cells. Like other nuclear hormone receptors, AR is a transcription factor, which is activated upon ligand binding in the cell cytoplasm. Activated AR enters the nucleus and regulates the transcription of genes involved in cell proliferation, survival, and differentiation. In this chapter, the endocrine mechanisms involve in the biosynthesis of androgen are discussed. Structural details of the androgen receptor, its changes in conformation upon ligand binding, various posttranslational modifications, and its coregulators are described. Specific roles of androgen/AR axis during the progression of prostate cancer and mechanisms by which AR activity is restored in prostate cancer cells of patients treated with androgen ablation therapy are discussed.

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Authors and Affiliations

  1. Departments of Urology and Biochemistry Molecular Biology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN, 55901, USA

    Kaustubh Datta Ph.D. & Donald J. Tindall Ph.D.

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  1. Kaustubh Datta Ph.D.
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  2. Donald J. Tindall Ph.D.
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Correspondence to Kaustubh Datta Ph.D. .

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  1. New York Presbyterian Hospital, Brady Urologic Health Center, Weill Cornell Medical Center, East 68th Street 525, New York, 10021, New York, USA

    Ashutosh Tewari

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Datta, K., Tindall, D.J. (2013). Endocrine Mechanisms, Androgen Receptor and Carcinogenesis, and Hormone Escape. In: Tewari, A. (eds) Prostate Cancer: A Comprehensive Perspective. Springer, London. https://doi.org/10.1007/978-1-4471-2864-9_3

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