Hormonal regulation of vitamin D receptor levels and osteocalcin synthesis in human osteosarcoma cells. 1,25(OH)2D3 was found to regulate its own receptor levels via an increase in corresponding mRNA levels in human osteoblast-like osteosarcoma cells (MG-63). In addition, exposure of the cells for 24h to dexamethasone, estradiol, retinoic acid, or triiodothyronine resulted in a dose-dependent accumulation of hVDR mRNA. Combination of 1,25(OH)2D3 with any other hormone used in this study did not result in an additive increase in hVDR mRNA levels. Progesterone or dihydrotestosterone did not influence hVDR mRNA levels. Of the studied hormones, only 1,25(OH)2D3 was alone able to stimulate the synthesis and secretion of osteocalcin. Compared with 1,25(OH)2D3, the combination of 1,25(OH)2D3 and retinoic acid resulted an increased synthesis of osteocalcin. In contrast, the combination of 1,25(OH)2D3 with dexamethasone, estradiol, or triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. A complex interaction of several different hormone receptors seems to occur within the regulatory regions of hVDR and osteocalcin genes, or at the level of translation, resulting, in each case, a finely adjusted vitamin D receptor and osteocalcin expression.