Loss of Sex-Specific Difference in Femoral Bone Parameters in Male Leptin Knockout Mice

Abstract

Sex-dependent differences were identified in the femoral bone parameters of male and female ob/ob (leptin knockout) mice compared with their C57BL/6 wild-type background strain. Total fat, lean weight and body weight were not different between adult male and female leptin knockout mice. However, leptin knockout males exhibited lower lean weights than C57BL/6 males. Peripheral quantitative computerized tomographic measurements at the femoral midshaft revealed that the normal differences in the periosteal circumference, endosteal circumference, total bone mineral content, and polar moment of inertia normally observed between adult male and female wild-type mice were lost between adult male and female ob/ob mice. Significant reductions in these bone parameters were seen in male ob/ob mice compared to male wild-type mice but not in female ob/ob mice compared to female wild-type mice. In prepubertal mice, there were no differences in phenotype and femoral bone parameters between males and females within any strain, suggesting sex hormone functions. Serum free testosterone levels were 5.6-fold higher in adult male ob/ob mice than in adult male C57BL/6 wild-type mice, and serum estradiol levels were 1.8- and 1.3-fold greater in adult male and female ob/ob mice, respectively, than in their wild-type counterparts. Androgen receptor gene expression was not different in femur-derived bone cells of male ob/ob mice compared with wild-type mice. The loss of sex-related differences in these bone parameters in adult male ob/ob mice might result from deficient signaling in the androgen signaling pathway and the fact that leptin functions are permissive for androgen effects on bone development.