Less-calcemic vitamin D analogs enhance creatine kinase specific activity and modulate responsiveness to gonadal steroids in rat skeletal tissues.
Vitamin D metabolites and analogs exert a variety of biological activities, such as regulation of cellular proliferation, differentiation and energy metabolism, exerted through the brain type isozyme of creatine kinase (CK) specific activity, serving to provide ATP generation. In the present study we assess the role of vitamin D in induction of CK in rat epiphyseal cartilage (Ep) and diaphyseal bone (Di). Skeletal tissues from female or male vitamin D-depleted rats showed lower CK than in vitamin D-replete rats in both Ep and Di. Moreover, estradiol-17beta (E2) or dihydrotestosterone (DHT), which increased CK in Ep and Di of intact female or male rats, respectively, stimulated CK in vitamin D-depleted rats to a much lower extent. Treatment of intact female rats for 1, 2 or 8 weeks with the less-calcemic vitamin D analogs JKF 1624F2-2 (JKF) or QW 1624F2-2 (QW) and the non-calcemic analog CB 1093 (CB), slightly affected CK, although there was an up-regulation of the E2- and DHT-induced CK response in Ep and Di from these rats. In intact female rats, all vitamin D analogs potentiated CK response to the SERM raloxifene (Ral) and tamoxifen (TAM) in these organs but the inhibitory effect of Ral or TAM on E2-induced CK was lost after this pre-treatment. CB induced a significant increase in estradiol receptor alpha (ERalpha) protein in both Ep and Di from intact female rats. Collectively, these results indicate that vitamin D analogs modulate CK in skeletal tissues and up-regulate its response and sensitivity to E2 and to SERM in these tissues, possibly via an increase in ERalpha protein. These results corroborate our previous studies in human bone cells, and further suggest that the vitamin D system plays an important physiological role in maintaining normal cell energy reservoir in the skeleton.
Somjen
D
D
Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel. dalias@tasmc.health.gov.il
Posner
G H
GH
Weisman
Y
Y
Kaye
A M
AM
D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004872:Ergocalciferols / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry*
D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D012739:Gonadal Steroid Hormones; D014807:Vitamin D; D003402:Creatine Kinase; D002118:Calcium