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Published in: Discover Oncology 3/2011

01-06-2011

Testosterone Regulates Tight Junction Proteins and Influences Prostatic Autoimmune Responses

Authors: Jing Meng, Elahe A. Mostaghel, Funda Vakar-Lopez, Bruce Montgomery, Larry True, Peter S. Nelson

Published in: Discover Oncology | Issue 3/2011

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Abstract

Testosterone and inflammation have been linked to the development of common age-associated diseases affecting the prostate gland including prostate cancer, prostatitis, and benign prostatic hypertrophy. We hypothesized that testosterone regulates components of prostate tight junctions which serve as a barrier to inflammation, thus providing a connection between age- and treatment-associated testosterone declines and prostatic pathology. We examined the expression and distribution of tight junction proteins in prostate biospecimens from mouse models and a clinical study of chemical castration, using transcript profiling, immunohistochemistry, and electron microscopy. We determined that low serum testosterone is associated with reduced transcript and protein levels of Claudin 4 and Claudin 8, resulting in defective tight junction ultrastructure in benign prostate glands. Expression of Claudin 4 and Claudin 8 was negatively correlated with the mononuclear inflammatory infiltrate caused by testosterone deprivation. Testosterone suppression also induced an autoimmune humoral response directed toward prostatic proteins. Testosterone supplementation in castrate mice resulted in re-expression of tight junction components in prostate epithelium and significantly reduced prostate inflammatory cell numbers. These data demonstrate that tight junction architecture in the prostate is related to changes in serum testosterone levels, and identify an androgen-regulated mechanism that potentially contributes to the development of prostate inflammation and consequent pathology.
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Metadata
Title
Testosterone Regulates Tight Junction Proteins and Influences Prostatic Autoimmune Responses
Authors
Jing Meng
Elahe A. Mostaghel
Funda Vakar-Lopez
Bruce Montgomery
Larry True
Peter S. Nelson
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Discover Oncology / Issue 3/2011
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-010-0063-1

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