The Effect of Androgen and Androgen Receptor（AR）Signaling on the Adipogenic Differentiation of D1 Mesenchymal Multipotent Progenitor Cells
| Autor: | Jyun-Ya Wang, 王俊雅 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Androgens (such as testosterone and 5α-dihydrotestosterone (DHT)) are the main male sex steroid hormones. Androgens not only affect the development of male phenotypes during embryogenesis and the sexual maturation at puberty, but also influence the functions of skin, bone, muscle, and brain. Androgen receptor (AR) belongs to the nuclear hormone receptor superfamily and mediates the action of androgen as a transcription factor to regulate it’s target gene expression. Studies have showed the regulatory role of A/AR signaling on adipogenic differentiation, but the molecular basis of androgen-related adipogenesis decrease is still unclear. In the present study, we examined the role of A/AR signaling and its molecular mechanism on adipocyte differentiation at the cellular and molecular level using D1 cell line, a multipotent mouse bone marrow stromal precursor cell line, as a model. We determined the expression and function of AR on the adipogenic differentiation of D1 cells by observing the molecular and cellular changes between undifferentiated and differentiated Dl cells. Our data showed that AR expressed in D1 cells, and had transcription activity which induced by DHT treatment. And we found the cell fate of D1 cells could be changed by DHT treatment, including the cell cycle, cell proliferation rate and adipogenic differentiation. We used Oil-red O staining to observed the cell morphology and used Q-PCR to demonstrated the expression change of adipogenic marker genes, and found that hormonal induction cocktail with dexamethasone (10-6M), insulin (0.01mg/ml), rosiglitazone (20μM) could induce D1 cells to adipocytes, and this adipogenesis could be repressd by DHT treatment. These data show that A/AR signaling pathway may play an important role in regulation on D1 cells adipogenesis process. Finally, we used the microarray experiment to found that some genes expression changed with DHT treatment in D1 cells, and these genes are involved in the signaling pathways favoring particular cell differentiation processes, including osteogenesis, myogenesis, chondrogenesis, but not the adipogenesis. We hope our study will provide new insights into the roles of A/AR in adipogenesis and its molecular mechanism. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|