title: Regulation of Sclerostin Production in Human Male Osteocytes by Androgens: Experimental and Clinical Evidence.
abstract: In this study we aimed to elucidate a possible role of T in the regulation of sclerostin, a glycoprotein secreted by osteocytes known to regulate bone mass. To this end, we evaluated the effect of T stimulation on sclerostin production and gene expression in human cultured osteocytes. In addition, we evaluated serum sclerostin levels in a cohort of 20 hypogonadal male patients, compared with 20 age-matched eugonadal controls. Stimulation with DHT decreased sclerostin expression in cultured osteocytes in a time- and dose-dependent manner. Confirming a direct androgen receptor-mediated effect on sclerostin production, flutamide coincubation and silencing of androgen receptor gene in osteocytes abolished the DHT effects. In addition, hypogonadal patients showed higher serum sclerostin levels with respect to controls (145.87 ± 50.83 pg/mL vs 84.02 ± 32.15 pg/mL; P < .001) and in both probands and controls, serum T levels were negatively correlated with sclerostin (R = -0.664, P = 0.007, and R = -0.447, P = .045, respectively). Finally, multiple stepwise regression analysis showed that T represented the only independent predictor of sclerostin levels. In conclusion, by showing a direct correlation between T and sclerostin, both in vivo and in vitro, this study adds further support to the emerging clinical and experimental studies focusing on sclerostin as a therapeutic target for osteoporosis treatment.
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Nisio
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Speltra
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Maria Santa
authors.initials: MS
authors.lastname: Rocca
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Taglialavoro
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferlin
authors.affiliation: Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000097:blood; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: C410798:AR protein, human; D048868:Adaptor Proteins, Signal Transducing; D000728:Androgens; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D011944:Receptors, Androgen; C422903:SOST protein, human; D013196:Dihydrotestosterone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone