Presentation Authors: Natasza Posielski*, Jordan Krieger, Madison, WI, Arthur Burnett, Haolin Chen, Barry Zirkin, Baltimore, MD, Brian Le, Madison, WI
Introduction: Osteocalcin (OC) has been shown to regulate testosterone (T) production in mice and may offer a promising target for treatment of hypogonadal men. Yet, the relationship between OC and T has received little attention in human studies. Our objective was to evaluate the relationship between OC and T in a prospective cohort of men and to use an established rat model to assess the effect of T supplementation on OC levels.
Methods: Men presenting to clinic for evaluation of hypogonadism were identified. Serum samples were assessed for total T, free T, sex hormone binding globulin (SHBG), bioavailable T, and OC. Similarly, T and OC levels were measured in Brown-Norway rats of varying ages. Testosterone levels were manipulated in the rat model using Translocator protein ligand (TSPO) to stimulate endogenous T production and silastic testosterone implants to increase exogenous T. Relationships between age, T and OC in humans and rats were evaluated using Pearsonâ€™s correlation, fisherâ€™s transformation, and t-tests.
Results: Ninety-two men (age 31-83y) were enrolled to participate in the study. The average total T and OC were 381.7 +/- 195.7 and 49.2 +/- 18.4, respectively. Total T and OC were positively correlated (R= 0.57, 95% CI 0.39-0.71). Free T and OC also correlated (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 ng/ml, p < 0.01). Thirty-six rats were included in the animal model. Aged rats were found to have lower total T (4.19 vs. 1.15 ng/ml, p < 0.01) and lower OC (1.81 vs. 0.97 ng/ml ,p < 0.01) than young rats. As in humans, T and OC were positively correlated (R= 0.69, 95% CI 0.86-0.89). Aged rats were treated with a transporter protein (TSPO) ligand with daily injections for 10 days. This resulted in increase in total T by 43% and no significant change in OC. Young rats received silastic T implants for 8 weeks which increased serum T levels to >2000ng/ml. Interestingly, seminiferous tubule T concentration decreased by 80% and serum OC also showed a significant decline (2.19 vs 1.70, p =0.06).
Conclusions: OC levels correlate with total and free T in both rats and men. Increasing endogenous testosterone production and administration of exogenous testosterone did not affect osteocalcin levels.
Source of Funding: Sexual Medicine Society of North America