Bayer School of Natural and Environmental Sciences
Bone, Estrogens, Estrone Sulfate, Glucocorticoids, NF-ÃŽÂºB Signaling, Steroid Sulfatase
The importance of estrogen in bone regulation is exemplified by the reduction in bone density at the onset of menopause. Post-menopausal women have low levels of estrogens, but high levels of inactive sulfated steroids. These can be converted to active steroids by steroid sulfatase (STS), which is a microsomal enzyme found in many tissues. STS desulfates common steroids such as dehydroepiandrosterone sulfate and estrone sulfate, the products of which can serve as precursors for active estrogens. We sought to characterize the activity and expression of STS in human bone cells with the idea that increasing STS expression in bone could offset low bone density.
STS activity was found to be relatively high in MG-63 pre-osteosarcoma cells, indicating that these cells can produce active estrogens from precursors. STS activity was blocked by the known inhibitors EMATE and 667 Coumate. In addition, cell growth was stimulated by addition of sulfated steroids.
STS activity and expression were examined in pre-osteoblastic and differentiated MG-63 cells over a 21-day period. STS activity and expression were higher in pre-osteoblastic cells than in differentiated cells. The STS decline was found to be due to the presence of the glucocorticoid dexamethasone in the differentiation medium. Inhibition of the glucocorticoid receptor with RU-486 blocked the decline in STS activity.
Results from a collaborator suggested that NF-ÃŽÂºB might regulate STS transcription. The NF-ÃŽÂºB activators LPS and PMA increased STS expression, which was lowered in the presence of the NF-ÃŽÂºB inhibitor BAY. Glucocorticoids and NF-ÃŽÂºB are antagonistic to each other with regard to immune responses. Thus, steroid sulfatase appears to be regulated like an immune response protein in pre-osteoblastic cells. The significance of this for bone physiology is unclear.
Our data indicate that steroid sulfatase is present in bone cells and that it can influence bone cell growth by converting inactive sulfated steroids to estrogenic forms. Furthermore, STS expression is regulated by glucocorticoid and NF-ÃŽÂºB pathways. Manipulation of STS expression via these pathways may lead to a potential treatment for osteoporosis.
Dias, N. (2015). Characterization and Regulation of Steroid Sulfatase in the Human MG-63 Pre-osteoblastic Cell Line (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1501