'Non-hypercalcemic' analogs of 1α,25 dihydroxy vitamin D augment the induction of creatine kinase B by estrogen and selective estrogen receptor modulators (SERMS) in osteoblast-like cells and rat skeletal organs

D. Somjen, A. Waisman, Y. Weisman, A. M. Kaye

Research output: Contribution to journalArticlepeer-review

Abstract

We have demonstrated previously that daily treatments for 3 days with the so-called 'non-hypercalcemic' analogs of 1α,25 dihydroxy vitamin D in ROS 17/2.8 osteoblast-like cells, stimulate the specific activity of creatine kinase BB (CK), and that such treatment with these analogs followed by a single treatment with gonadal steroids, upregulates responsiveness and sensitivity to estradiol 17β (E2) for the induction of CK. This study was designed to determine if these same 'non-hypercalcemic' vitamin D analogs could upregulate in vivo the response to E2 and whether substitution of selective estrogen receptor modulators (SERMS) for E2 would result in the same upregulation. We found that one week or 2 weeks pretreatment of prepubertal rats with vitamin D analogs led to increased induction of CK by E2 and by the SERMS tamoxifen, tamoxifen methiodide and raloxifene, in epiphysis and diaphysis of the femur but not in the uterus. However, in contrast to their antiestrogenic activity in the uterus, there was no inhibition of E2 action by the SERMS in skeletal tissues. The induction of mRNA for ckb in ROS 17/2.8 cells by E2 or SERMS was demonstrated only after vitamin D pretreatment; there was no inhibition of E2 induction by SERMS. Antagonists of vitamin D dependent calcium transport (transcaltachia) did not inhibit stimulation by vitamin D analogs. These results support the involvement of a nuclear mechanism in the upregulation of induction of CK by E2, which may be due, in part, to the ability of vitamin D to increase estrogen receptor(s).

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume72
Issue number1-2
DOIs
StatePublished - 2000

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