Endocrine Abstracts

Vitamin D metabolites modulate creatine kinase specific activity (CK) in cultured skeletal cells. In this study we assess the effect of vitamin D metabolites on CK in rat epiphyseal cartilage (Ep) and diaphyseal bone (Di). Female or male Wistar- derived rats were used either as intact or after gonadectomy (Ovx or cast respectively), and treatments started 2 weeks post surgery. Rats were injected daily for 1, 2 or 8 weeks with the less-calcemic vitamin D analogs CB 1093 (CB), JKF 1624F₂-2 (JKF) or QW 1624F₂-2 (QW) and 24hrs after the last analog injection, rats were injected with E₂, raloxifene (Ral) or tamoxifen (TAM) or both in females or dihydrotestosterone (DHT) in males, and organs were collected for CK measurements and western blot analysis for estradiol receptor ( (ERα) 24hrs after last injection. CK was lower in Ep and Di from vitamin D- depleted than in vitamin D- replete rats. Moreover E₂ or DHT, which increases CK in Ep and Di of intact female or male rats, stimulated CK to a much lower extent in vitamin D- depleted rats. Treatment of intact female rats for 2 or 8 weeks with JKF or QW, upregulated the E₂ – or DHT- response of CK in Ep and Di, without affecting constituent levels. All vitamin D analogs enhanced the CK response to Ral and TAM in these organs, but the inhibitory effect of Ral or TAM on E₂-induced CK was lost. CB induced also ER( protein in Ep and Di from intact and Ovx female rats. In conclusion, vitamin D induces CK and upregulates the response and sensitivity of CK to E₂ and SERMs, possibly via increased ER( protein. These results corroborate our in vitro studies in human bone cells and provide evidence that vitamin D is crucial to maintain normal skeletal energy metabolism.