Elucidation of Androgen Action on the Diifferentiatioa of Bone Marrow Stromal Cells

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Teikyo University
• Principal Investigator: OKAZAKI Ryo Teikyo University, School of Medicine, Associate Professor, 医学部, 助教授 (10297137)
• Project Period (FY): 2003 – 2004
• Keywords: Androgen / Adinocyte / Osteoblast / PPARgamma / Wnt / Estrogen

Research Abstract

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.