Estrogens and bladder outlet obstruction

Li, Xiangdong; Rahman, Nafis

doi:10.1016/j.jsbmb.2009.10.014

Cited by 5 publications

(4 citation statements)

References 96 publications

(107 reference statements)

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“…Our data suggest that, beside classic estrogen receptors, also GPR30/GPER1 should be considered as a possible mediator of estrogen action in bladder. This finding will explain the lack of a specific bladder phenotype in mice lacking ERα, ERβ, but not in those overexpressing aromatase [10,11]. However, our results do not provide a clear elucidation on the specific involvement of each estrogen receptor type in 17β‐estradiol‐ and G1‐induced effects in bladder smooth muscle.…”

Section: Discussioncontrasting

confidence: 62%

“…Clinical studies showing that androgen deficiency is associated with male bladder instability are in keeping with this view [6,7,58,59]. Since an altered estrogen/androgen ratio characterize several physiological and pathological conditions, often associated to bladder hyperactivity and LUTS, as aging, obesity, and metabolic syndrome [2,11], it is possible that a relative hyperestrogenism might induce bladder overactivity, through an activation of the RhoA/ROCK pathway. The relative contribution of genomic vs. nongenomic estrogen receptor activation in human bladder needs to be addressed in further studies.…”

Section: Discussionmentioning

confidence: 80%

“…Accordingly, in aromatase‐overexpressing transgenic C57B1 mice (AROM+) there is a phenotype characterized by severe bladder outlet obstruction [10] and morphological changes in detrusor smooth muscle (25). AROM+ phenotype is characterized by reduced androgen and highly increased estrogen plasma levels [11], suggesting a role for estrogen in the development of bladder dysfunction. In accordance to these observations, an imbalance between the androgen and estrogen ratio also has been reported in patients suffering from BPH [7].…”

Section: Introductionsmentioning

confidence: 99%

“…In various animal species estrogen receptors (ERs: ERα and ERβ) are shown to be expressed in central nervous structures involved in micturition [12], as well as in the bladder and urethra [13,14]. No specific bladder phenotype has been reported in mice deficient for ERα and ERβ[11]. In addition to classic ERs, which are members of the nuclear receptor family involved in regulating genomic action of estrogens, in the recent past, an orphan receptor, GPR30/GPER1, has been shown to be involved in mediating some estrogen actions, in particular the nongenomic ones [15].…”

Section: Introductionsmentioning

confidence: 99%

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Sex Steroid Receptors in Male Human Bladder: Expression and Biological Function

Chavalmane

Comeglio

Morelli

et al. 2010

The Journal of Sexual Medicine

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Introduction In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens. Within the bladder, LUTS are linked to RhoA/Rho-kinase (ROCK) pathway overactivity. Aim To investigate the effects of changing sex steroids on bladder smooth muscle. Methods ERα, ERβ, GPR30/GPER1 and aromatase mRNA expression was analyzed in male genitourinary tract tissues, and cells isolated from bladder, prostate, and urethra. Estrogen and G1 effect on RhoA/ROCK signaling output like cell migration, gene expression, and cytoskeletal remodeling, and [Ca2+]i was also studied in hB cells. Contractile studies on bladder strips from castrated male rats supplemented with estradiol and testosterone was also performed. Main Outcome Measures The effects of classical (ERα, ERβ) and nonclassical (GPR30/GPER1) estrogen receptor ligands (17β-estradiol and G1, respectively) and androgens on RhoA/ROCK-.mediated cell functions were studied in hB cells. Contractility studies were also performed in bladder strips from castrated male rats supplemented with testosterone or estradiol. Results Aromatase and sex steroid receptors, including GPR30, were expressed in human bladder and mediates several biological functions. 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. Estrogen-, but not androgen-supplementation to castrated rats increased sensitivity to the ROCK inhibitor, Y-27632 in isolated bladder strips. In hB cells, testosterone elicited effects similar to estrogen, which were abrogated by blocking its aromatization through letrozole. 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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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 80%