Activation of Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) by Rosiglitazone Suppresses Components of the Insulin-Like Growth Factor Regulatory System in Vitro and in Vivo Export

@article{citeulike:3874814, abstract = {Rosiglitazone (Rosi) belongs to the class of thiazolidinediones (TZDs) that are ligands for peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}). Stimulation of PPAR{gamma} suppresses bone formation and enhances marrow adipogenesis. We hypothesized that activation of PPAR{gamma} down-regulates components of the IGF regulatory system, leading to impaired osteoblast function. Rosi treatment (1 {micro}M) of a marrow stromal cell line (UAMS-33) transfected with empty vector (U-33/c) or with PPAR{gamma}2 (U-33/{gamma}2) were analyzed by microarray. Rosi reduced IGF-I, IGF-II, IGFBP-4, and the type I and II IGF receptor (IGF1R and IGF2R) expression at 72 h in U-33/{gamma}2 compared with U-33/c cells (P < 0.01); these findings were confirmed by RT-PCR. Rosi reduced secreted IGF-I from U-33/{gamma}2 cells by 75\% (P < 0.05). Primary marrow stromal cells (MSCs) extracted from adult (8 months) and old (24 months) C57BL/6J (B6) mice were treated with Rosi (1 {micro}M) for 48 h. IGF-I, IGFBP-4, and IGF1R transcripts were reduced in Rosi-treated MSCs compared with vehicle (P < 0.01) and secreted IGF-I was also suppressed (P < 0.05). B6 mice treated with Rosi (20 mg/kg{middle dot}d) for short duration (i.e. 4 d), and long term (i.e. 7 wk) had reduced serum IGF-I; this was accompanied by markedly suppressed IGF-I transcripts in the liver and peripheral fat of treated animals. To determine whether Rosi affected circulating IGF-I in humans, we measured serum IGF-I, IGFBP-2, and IGFBP-3 at four time points in 50 postmenopausal women randomized to either Rosi (8 mg/d) or placebo. Rosi-treated subjects had significantly lower IGF-I at 8 wk than baseline (-25\%, P < 0.05), and at 16 wk their levels were reduced 14\% vs. placebo (P = 0.15). We conclude that Rosi suppresses IGF-I expression in bone and liver; these changes could affect skeletal acquisition through endocrine and paracrine pathways. 10.1210/en.2006-1121}, author = {Lecka-Czernik, B. and Ackert-Bicknell, C. and Adamo, M. L. and Marmolejos, V. and Churchill, G. A. and Shockley, K. R. and Reid, I. R. and Grey, A. and Rosen, C. J.}, citeulike-article-id = {3874814}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/en.2006-1121}, citeulike-linkout-1 = {http://endo.endojournals.org/cgi/content/abstract/148/2/903}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17122083}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17122083}, day = {1}, doi = {10.1210/en.2006-1121}, journal = {Endocrinology}, keywords = {igf-1, ppar-gamma}, month = {February}, number = {2}, pages = {903--911}, posted-at = {2009-01-12 02:34:38}, priority = {3}, title = {Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) by Rosiglitazone Suppresses Components of the Insulin-Like Growth Factor Regulatory System in Vitro and in Vivo}, url = {http://dx.doi.org/10.1210/en.2006-1121}, volume = {148}, year = {2007} }

TY - JOUR ID - citeulike:3874814 L3 - citeulike-article-id:3874814 N2 - Rosiglitazone (Rosi) belongs to the class of thiazolidinediones (TZDs) that are ligands for peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}). Stimulation of PPAR{gamma} suppresses bone formation and enhances marrow adipogenesis. We hypothesized that activation of PPAR{gamma} down-regulates components of the IGF regulatory system, leading to impaired osteoblast function. Rosi treatment (1 {micro}M) of a marrow stromal cell line (UAMS-33) transfected with empty vector (U-33/c) or with PPAR{gamma}2 (U-33/{gamma}2) were analyzed by microarray. Rosi reduced IGF-I, IGF-II, IGFBP-4, and the type I and II IGF receptor (IGF1R and IGF2R) expression at 72 h in U-33/{gamma}2 compared with U-33/c cells (P < 0.01); these findings were confirmed by RT-PCR. Rosi reduced secreted IGF-I from U-33/{gamma}2 cells by 75% (P < 0.05). Primary marrow stromal cells (MSCs) extracted from adult (8 months) and old (24 months) C57BL/6J (B6) mice were treated with Rosi (1 {micro}M) for 48 h. IGF-I, IGFBP-4, and IGF1R transcripts were reduced in Rosi-treated MSCs compared with vehicle (P < 0.01) and secreted IGF-I was also suppressed (P < 0.05). B6 mice treated with Rosi (20 mg/kg{middle dot}d) for short duration (i.e. 4 d), and long term (i.e. 7 wk) had reduced serum IGF-I; this was accompanied by markedly suppressed IGF-I transcripts in the liver and peripheral fat of treated animals. To determine whether Rosi affected circulating IGF-I in humans, we measured serum IGF-I, IGFBP-2, and IGFBP-3 at four time points in 50 postmenopausal women randomized to either Rosi (8 mg/d) or placebo. Rosi-treated subjects had significantly lower IGF-I at 8 wk than baseline (-25%, P < 0.05), and at 16 wk their levels were reduced 14% vs. placebo (P = 0.15). We conclude that Rosi suppresses IGF-I expression in bone and liver; these changes could affect skeletal acquisition through endocrine and paracrine pathways. 10.1210/en.2006-1121 IS - 2 JF - Endocrinology EP - 911 TI - Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) by Rosiglitazone Suppresses Components of the Insulin-Like Growth Factor Regulatory System in Vitro and in Vivo VL - 148 SP - 903 KW - igf-1 KW - ppar-gamma AU - Lecka-Czernik, B AU - Ackert-Bicknell, C AU - Adamo, ML AU - Marmolejos, V AU - Churchill, GA AU - Shockley, KR AU - Reid, IR AU - Grey, A AU - Rosen, CJ PY - 2007/02/01/ UR - http://dx.doi.org/10.1210/en.2006-1121 ER -