"Non-hypercalcemic'' analogs of 1 alpha,25 dihydroxy vitamin D augment theinduction of creatine kinase B by estrogen and selective estrogen receptormodulators (SERMS) in osteoblast-like cells and rat skeletal organs

We have demonstrated previously that daily treatments for 3 days with the s o-called "non-hypercalcemic" analogs of 1 alpha,25 dihydroxy vitamin D in R OS 17/2.8 osteoblast-like cells, stimulate the specific activity of creatin e kinase BE (CK), and that such treatment with these analogs followed by a single treatment with gonadal steroids, upregulates responsiveness and sens itivity to estradiol 17 beta (E-2) for the induction of CK. This study was designed to determine if these same "non-hypercalcemic" vitamin D analogs c ould upregulate in vivo the response to E-2 and whether substitution of sel ective estrogen receptor modulators (SERMS) for E-2 would result in the sam e upregulation. We found that one week or 2 weeks pretreatment of prepubert al rats with vitamin D analogs led to increased induction of CK by E-2 and by the SERMS tamoxifen, tamoxifen methiodide and raloxifene, in epiphysis a nd diaphysis of the femur but not in the uterus. However, in contrast to th eir antiestrogenic activity in the uterus, there was no inhibition of E-2 a ction by the SERMS in skeletal tissues. The induction of mRNA for ckb in RO S 17/2.8 cells by E-2 or SERMS was demonstrated only after vitamin D pretre atment; there was no inhibition of E-2 induction by SERMS. Antagonists of v itamin D dependent calcium transport (transcaltachia) did not inhibit stimu lation by vitamin D analogs. These results support the involvement of a nuc lear mechanism in the upregulation of induction of CK by E-2, which may be due, in part, to the ability of vitamin D to increase estrogen receptor(s). (C) 2000 Elsevier Science Ltd. All rights reserved.