ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2010) 22 P737 
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Expression and biological function of sex steroid receptors in male human bladder

Linda Vignozzi1, Aravinda K Chavalmane1, Paolo Comeglio1, Annamaria Morelli1, Sandra Filippi1, Benedetta Fibbi1, Gabriella B Vannelli3 & Mario Maggi1

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In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected co-morbidities, such as hypogonadism, obesity and metabolic syndrome, which are essentially characterized by an unbalance between circulating androgens and estrogens. Within the bladder, LUTS have been linked to overactivity of the RhoA/ROCK pathway. Here we investigate the effects of changing sex steroids on bladder smooth muscle. The effects of androgens and classical (ERα, ERβ) and non-classical (GPR30/GPER1) estrogen receptor ligands (17β-estradiol and G1, respectively) on RhoA/ROCK- mediated cell functions were studied in human bladder smooth muscle (hB) cells. Contractility studies were also performed in bladder strips from castrated male rats supplemented with testosterone or estradiol. Aromatase and sex steroid receptors, including GPR30, were expressed in human bladder tissue and hB cells and mediates several biological functions. In particular, both 17β-estradiol and G1 activated calcium transients and induced RhoA/ROCK signaling (cell migration, cytoskeleton remodeling and smooth muscle gene expression). RhoA/ROCK inhibitors blunted these effects. In isolated bladder strips, estrogen-, but not androgen-, supplementation to castrated male rats increased sensitivity to the specific ROCK inhibitor, Y27632. In hB cells, testosterone elicited effects similar to estrogen, which were abrogated by blocking its aromatisation through letrozole. In conclusion, our data indicate for the first time that estrogen- more than androgen- receptors up-regulate RhoA/ROCK signaling. Since an altered estrogen/androgen ratio characterizes conditions, such as aging, obesity and metabolic syndrome, often associated to LUTS, we speculate that a relative hyperestrogenism may induce bladder overactivity through the up regulation of RhoA/ROCK pathway.

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