title: Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia.
abstract: The bioactive form of vitamin D, 1,25-dihydroxyvitamin D(3), is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, and modulates a variety of biological functions. The VDR is expressed by most cell types, including cells of the urogenital system, such as prostate and bladder cells. In particular, the prostate is a target organ of VDR agonists and represents an extrarenal synthesis site of 1,25-dihydroxyvitamin D(3). We have analyzed the capacity of VDR agonists to treat benign prostatic hyperplasia (BPH), a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic component responsible for urinary irritative symptoms, and an inflammatory component. Data reviewed here demonstrate that VDR agonists, and notably elocalcitol, reduce the static component of BPH by inhibiting the activity of intraprostatic growth factors downstream of the androgen receptor, the dynamic component by targeting the RhoA/ROCK pathway in prostate and bladder cells, and the inflammatory component by targeting the NF-kappaB pathway.
authors.affiliation: Intercept Pharmaceuticals, Corciano (Perugia), Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Adorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penna
authors.forename: Benedetta
authors.initials: B
authors.lastname: Fibbi
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000819:agonists*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D006133:Growth Substances; D018167:Receptors, Calcitriol; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D054460:rho-Associated Kinases