PD36-08 LOW OSTEOCALCIN LEVELS ARE AN INDEPENDENT FACTOR ASSOCIATED WITH ANDROGEN DEFICIENCY (2015)

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2015PD36-08 LOW OSTEOCALCIN LEVELS ARE AN INDEPENDENT FACTOR ASSOCIATED WITH ANDROGEN DEFICIENCY Brian Le, Haolin Chen, Kevin Billups, Arthur L. Burnett, and Barry Zirkin Brian LeBrian Le More articles by this author , Haolin ChenHaolin Chen More articles by this author , Kevin BillupsKevin Billups More articles by this author , Arthur L. BurnettArthur L. Burnett More articles by this author , and Barry ZirkinBarry Zirkin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2257AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Osteocalcin (OC) is a bone turnover marker that has recently been found in mice to be a novel regulator of testosterone production through a previously orphaned G-protein coupled receptor. Seeking to characterize OC's role in age-related androgen deficiency we conducted a bench to bedside study using serum samples from a prospective cohort of men being evaluated for hypogonadism and further investigated these findings in a rat model of androgen deficiency. METHODS We prospectively enrolled men who presented to the Johns Hopkins Men's Health Clinic who were being evaluated for symptomatic hypogonadism. Serum T, free T, SHBG, bioavailable T, and OC were obtained from blood samples and assayed using commercial laboratory techniques. Data were analyzed using Pearson's correlation, fisher's transformation and t-tests. Brown-Norway (BN) rats, like humans, have an age-related decline in testosterone production. We hypothesized that in our rat model of age-related hypogonadism OC levels would be lower in older rats, like in humans. We then altered serum testosterone levels acutely in vivo to examine its effects on serum OC. Lastly, we injected recombinant rat OC to examine its effects on T levels. RESULTS Ninety-two men were enrolled to participate in this prospective longitudinal cohort study. Total T and OC demonstrated a positive linear relationship with a correlation coefficient of R=0.57 (95% CI 0.39-0.71). Free T and OC were also correlated at R=0.47 (95% CI 0.27-0.63). Men with total T 350 ng/dl or less had significantly lower OC levels than eugonadal men (13.1 vs. 19.1 p<0.01). Similar to humans, in aged rats serum testosterone was lower compared to young rats (4.19 vs. 1.15 ng/ml p< 0.01). Serum OC levels were also lower in aged rats (1.81 vs. 0.97 ng/ml P<0.01). In old rats treated with a transporter protein (TSPO) ligand, serum testosterone increased 43%, while serum OC levels remained unchanged (0.93 vs.090 p = 0.93). In young rats treated with silastic T implants, serum OC levels decreased (2.19 vs 1.70 p =0.06) demonstrating OC is independent of T. Direct injection of recombinant OC did not acutely raise serum T levels versus placebo. CONCLUSIONS Androgen deficiency, and in particular lower free T, is associated with lower osteocalcin levels. In rats as well as humans, OC strongly correlates with serum T levels, and appears to do so independently of perturbations of T levels. This provides evidence to OC being a potential novel target pathway for treating androgen deficiency. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e768 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian Le More articles by this author Haolin Chen More articles by this author Kevin Billups More articles by this author Arthur L. Burnett More articles by this author Barry Zirkin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...