Testosterone Regulates Tight Junction Proteins and Influences Prostatic Autoimmune Responses

被引：45

作者：

Meng J. ^{[1
]}

Mostaghel E.A. ^{[1
,2
]}

Vakar-Lopez F. ^{[3
]}

Montgomery B. ^{[2
]}

True L. ^{[3
]}

Nelson P.S. ^{[1
,2
,3
]}

机构：

[1] Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, D4-100

[2] Department of Oncology, University of Washington, Seattle, WA

[3] Department of Pathology, University of Washington, Seattle, WA

来源：

Hormones and Cancer | 2011年 / 2卷 / 3期

关键词：

Claudin; Inflammation; Testosterone supplementation; Tight junction;

D O I：

10.1007/s12672-010-0063-1

中图分类号：

学科分类号：

摘要：

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. © 2011 Springer Science+Business Media, LLC.

引用

页码：145 / 156

页数：11

共 50 条

[41]

Palapattu G.S., Sutcliffe S., Bastian P.J., Et al., Prostate carcinogenesis and inflammation: emerging insights, Carcinogenesis, 21, (2004)

[42]

de Marzo A.M., Marchi V.L., Epstein J.I., Nelson W.G., Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis, Am J Pathol, 155, pp. 1985-1992, (1999)

[43]

Nakayama M., Bennett C.J., Hicks J.L., Et al., Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection, Am J Pathol, 163, pp. 923-933, (2003)

[44]

de Marzo A.M., Platz E.A., Sutcliffe S., Et al., Inflammation in prostate carcinogenesis, Nat Rev Cancer, 7, pp. 256-269, (2007)

[45]

Ponniah S., Arah I., Alexander R.B., PSA is a candidate self-antigen in autoimmune chronic prostatitis/chronic pelvic pain syndrome, Prostate, 44, pp. 49-54, (2000)

[46]

Schneeberger E.E., Lynch R.D., Structure, function, and regulation of cellular tight junctions, Am J Physiol, 262, pp. 647-661, (1992)

[47]

Bhasin S., Buckwalter J.G., Testosterone supplementation in older men: a rational idea whose time has not yet come, J Androl, 22, pp. 718-731, (2001)

[48]

Jemal A., Siegel R., Ward E., Hao Y., Xu J., Thun M.J., Cancer statistics, 2009, CA Cancer J Clin, 59, pp. 225-249, (2009)

[49]

Karazindiyanoglu S., Cayan S., The effect of testosterone therapy on lower urinary tract symptoms/bladder and sexual functions in men with symptomatic late-onset hypogonadism, Aging Male, 11, pp. 146-149, (2008)

[50]

Kalinchenko S., Vishnevskiy E.L., Koval A.N., Mskhalaya G.J., Saad F., Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: a pilot study, Aging Male, 11, pp. 57-61, (2008)

← 1 2 3 4 5 →