|Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2004 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 2003 : ¥1,800,000 (Direct Cost : ¥1,800,000)
In estrogen receptor (ER) a or b overexpressed bone marrow stromal cells, 5α -dehydrotestosterone(DHT) and dehydroepiandrostendinoe(DHEA) inhibit adipocytic differentiation whereas promote osteoblastic differentiation. These effects of A were not observed in wild-type cells that express equivalent level of AR. A effects were blocked by an estrogen antagonist, IC1182780, but not by A antagonist, hydroxyfluatmide, suggesting A effects are mediated by ER. Indeed, in these cells, DHT and DHEA enhanced estrogen responsive reporter gene activity, of which mechanisms are currently under investigation. Because A decreased expression of PPARg2, we postulated aforementioned A action may be mediated by the decrease in PPARg action. We tested A effects on a PPARg responsive reporter (1xPPRE-luc). However, in the cell system currently used, this reporter did not respond enough to a PPARg agonist, troglitazone (Tro). More responsive reporter genes were developed and currently tested for their responsiveness. Also tested were, the possible involvement of Wnt system. So far, Wnt 10b was constitutively expressed in stromal cells and down-regulated by Tro. Wnt responsive reporter (TOP-Flash) activity, however, appeared not to be regulated by A.