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Published on: January 16, 2013
Testosterone regulates tight junction proteins and influences prostatic autoimmune responses
Jing Meng1, Elahe A Mostaghel, Funda Vakar-Lopez
1Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, D4-100, 1100 Fairview Ave. N, Seattle, WA 98109-1024, USA.
Hormones & Cancer
|July 16, 2011
Summary
Testosterone decline impairs prostate barrier function, increasing inflammation and disease risk. Restoring testosterone levels repairs this barrier and reduces prostate inflammation.
Area of Science:
- Urology
- Endocrinology
- Immunology
Background:
- Testosterone decline is linked to prostate diseases like cancer and BPH.
- Prostate inflammation may result from impaired barrier function due to low testosterone.
Purpose of the Study:
- To investigate if testosterone regulates prostate tight junctions, acting as a barrier to inflammation.
- To explore the link between testosterone levels, tight junction integrity, and prostatic pathology.
Main Methods:
- Analysis of prostate biospecimens from mouse models and human clinical studies (chemical castration).
- Utilized transcript profiling, immunohistochemistry, and electron microscopy to assess tight junction proteins.
- Examined the correlation between testosterone levels, tight junction protein expression, and inflammatory cell infiltration.
Main Results:
- Low serum testosterone correlated with reduced Claudin 4 and Claudin 8 expression and defective tight junction structure.
- Testosterone deprivation led to increased mononuclear inflammatory infiltrate and an autoimmune response.
- Testosterone supplementation in castrated mice restored tight junction proteins and reduced prostate inflammation.
Conclusions:
- Prostate tight junction architecture is dependent on serum testosterone levels.
- Androgen-regulated mechanisms involving tight junctions play a role in prostate inflammation and disease development.
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