抄録
Glucocorticoids are produced in the adrenal cortex under the strict control of the hypothalamus-pituitary-adrenal axis and exert a variety of biological actions including the regulation of glucose and lipid metabolism, electrolyte balance, and modulation of the immune, cardiovascular, and central nervous system. Pharmacologically, glucocorticoids are estimated to be used long-term by 0.5-1% of the general population and up to 2.5% of older adults. Despite the established role of glucocorticoids in controlling short-term inflammation, and despite emerging evidence supporting a disease-modifying role in various autoimmune disorders, concern for adverse events associated with glucocorticoids often limits their use. The glucocorticoid compounds bind the glucocorticoid receptor (GR), which is a member of the nuclear receptor superfamily, and elicit their pharmacological actions. Recent progress in molecular biology of the GR has extended our understanding of their mechanism of action, however, the molecular basis for the side effects have not been fully clarified. Indeed, dissociation of their therapeutic effects and adverse reactions is still one of the most challenging clinical issues to be solved.
In this lecture, I will focus on the recent understanding of the molecular mechanism of glucocorticoid action and our recent work with ursodeoxycholic acid and cortivazol and discuss rationale to develop novel glucocorticoid-like compounds.
