Steroid hormones like cortisol, vitamin D and estradiol are responsible for principle events associated with bone formation and resorption. The action of these hormones in bone is reflected by the specific regulation of genes in bone cells, thereby affecting bone formation and resorption.
Glucocorticoids exert a suppressive effect on bone formation.
Increasing levels of glucocorticoids results in the development of osteoporosis in the long term. An example of a gene which is negatively regulated by glucocorticoids in bone is the gene for the major noncollagenous bone protein osteocalcin. In vitro analysis has identified a glucocorticoid receptor binding element in the human osteocalcin promoter that overlaps a functionally important basic transcription element, the TATA box. The project the function of this dual element and mechanistic aspects of the glucocorticoid dependent transrepression have been characterized in this thesis work. This mutation was shown to transform the transrepressive effect of wild-type GR, acting on reporter constructs containing a negative composite GRE or a negative tethering GRE, into an activating function.