Endocrine Abstracts

We have previously demonstrated that rat bone cells in vivo and in vitro, responded sex-specifically to gonadal steroids in stimulation of the specific activity of creatine kinase (CK). Pretreatment with vitamin D analogs upregulated the sex-specific responsiveness and sensitivity to gonadal steroids. We also found that mice cultured femoral bone marrow (BM) in the presence of dexamethasone (DEX), 1.25(OH)2D3 (1.25D) or both, differentiated into osteoblast-like cells (Obs), acquiring sex-specific responsiveness to gonadal steroids. We now examined the effect of age, sex and vitamin D non-hypercalcemic analogs on differentiation of rat femoral BM into Obs. In female or male, BM from intact but not gonadectomized rats DEX and DEX+1.25D increased the constitutive levels of CK. BM from old females showed lower stimulation of CK than BM from young females by estradiol-17β (E2) or raloxifene (Ral) in the presence of both DEX and 1.25D. The non-hypercalcemic analogs of vitamin D: CB 1093 (CB), EB 1089 (EB) and MC 1288 (MC) were more effective than 1.25D in both age groups in stimulating CK in the absence of DEX. In the presence of DEX, CK was further increased with the same differential effectiveness. BM from gonadectomized male or female rats, lost the sex-specific response namely responding to both E2 and dihydrotestosterone (DHT). BM derived from intact and gonadectomized males and females, growing with DEX or DEX+1.25D showed increased activity of basal alkaline phodphatase (AP) with no stimulation by gonadal steroids. These findings suggest that manipulation of the hormonal milieu in early stages of differentiation into Obs determines the subsequent selective responsiveness of the developing bone tissue to sex steroids. Non-calcemic vitamin D analogs were more effective than 1.25D and showed activity even in the absence of DEX and may be applied for bone tissue engineering.