title: TGF-β mediates suppression of adipogenesis by estradiol through connective tissue growth factor induction.
abstract: In the bone marrow cavity, adipocyte numbers increase, whereas osteoblast progenitor numbers decrease with aging. Because adipocytes and osteoblasts share a common progenitor, it is possible that this shift is due to an increase in adipocyte-lineage cells at the expense of osteoblast-lineage commitment. Estrogens inhibit adipocyte differentiation, and in both men and women, circulating estrogens correlate with bone loss with aging. In bone cells, estrogens stimulate expression of TGF-β and suppress mesenchymal cell adipogenesis. Using a tripotential mesenchymal cell line, we have examined whether estradiol suppression of adipocyte differentiation is due to stimulation of TGF-β and the mechanism by which TGF-β suppresses adipogenesis. We observed that estradiol-mediated suppression of adipogenic gene expression required at least 48 h treatment. TGF-β expression increased within 24 h of estradiol treatment, and TGF-β inhibition reversed estradiol influences on adipogenesis and adipocyte gene expression. Connective tissue growth factor (CTGF) mediates TGF-β suppression of adipogenesis in mouse 3T3-L1 cells. CTGF expression was induced within 24 h of TGF-β treatment, whereas estradiol-mediated induction required 48 h treatment. Moreover, estradiol-mediated induction of CTGF was abrogated by TGF-β inhibition. These data support that estradiol effects on adipogenesis involves TGF-β induction, which then induces CTGF to suppress adipogenesis.
authors: Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors: Ashok
authors: A
authors: Kumar
authors: Ming
authors: M
authors: Ruan
authors: Kari
authors: K
authors: Clifton
authors: Farhan
authors: F
authors: Syed
authors: Sundeep
authors: S
authors: Khosla
authors: Merry Jo
authors: MJ
authors: Oursler
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis*; D017931:DNA Primers / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C526318:CCN2 protein, mouse; D017931:DNA Primers; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor; D004958:Estradiol