| Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. | |
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MedLine Citation:
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PMID: 18801408 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms by which androgens regulate fat mass are poorly understood. Although testosterone has been reported to increase lipolysis and inhibit lipid uptake, androgen effects on proliferation and differentiation of human mesenchymal stem cells (hMSCs) and preadipocytes have not been studied. Here, we investigated whether dihydrotestosterone (DHT) regulates proliferation, differentiation, or functional maturation of hMSCs and human preadipocytes from different fat depots. DHT (0-30 nM) dose-dependently inhibited lipid accumulation in adipocytes differentiated from hMSCs and downregulated expression of aP2, PPARgamma, leptin, and C/EBPalpha. Bicalutamide attenuated DHT's inhibitory effects on adipogenic differentiation of hMSCs. Adipocytes differentiated in presence of DHT accumulated smaller oil droplets suggesting reduced extent of maturation. DHT decreased the incorporation of labeled fatty acid into triglyceride, and downregulated acetyl CoA carboxylase and DGAT2 expression in adipocytes derived from hMSCs. DHT also inhibited lipid accumulation and downregulated aP2 and C/EBPalpha in human subcutaneous, mesenteric and omental preadipocytes. DHT stimulated forskolin-stimulated lipolysis in subcutaneous and mesenteric preadipocytes and inhibited incorporation of fatty acid into triglyceride in adipocytes differentiated from preadipocytes from all fat depots. CONCLUSIONS: DHT inhibits adipogenic differentiation of hMSCs and human preadipocytes through an AR-mediated pathway, but it does not affect the proliferation of either hMSCs or preadipocytes. Androgen effects on fat mass represent the combined effect of decreased differentiation of fat cell precursors, increased lipolysis, and reduced lipid accumulation. |
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Authors:
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Vandana Gupta; Shalender Bhasin; Wen Guo; Rajan Singh; Rika Miki; Pratibha Chauhan; Karen Choong; Tamara Tchkonia; Nathan K Lebrasseur; John N Flanagan; James A Hamilton; Jason C Viereck; Navjot S Narula; James L Kirkland; Ravi Jasuja |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-08-28 |
Journal Detail:
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Title: Molecular and cellular endocrinology Volume: 296 ISSN: 0303-7207 ISO Abbreviation: Mol. Cell. Endocrinol. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-25 Completed Date: 2009-02-20 Revised Date: 2010-09-21 |
Medline Journal Info:
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Nlm Unique ID: 7500844 Medline TA: Mol Cell Endocrinol Country: Ireland |
Other Details:
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Languages: eng Pagination: 32-40 Citation Subset: IM |
Affiliation:
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Department of Medicine, Boston University, School of Medicine, Boston Medical Center, Boston, MA 02118, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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drug effects*,
physiology Adipogenesis / drug effects Adult Animals Cell Differentiation / drug effects* Cell Proliferation / drug effects* Cells, Cultured Dihydrotestosterone / pharmacology* Epididymis Humans Lipolysis / drug effects Male Mesenchymal Stem Cells / drug effects*, physiology Mice Mice, Inbred C57BL Middle Aged Orchiectomy Receptors, Androgen / physiology Signal Transduction / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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AG14369/AG/NIA NIH HHS; DK49296/DK/NIDDK NIH HHS; DK56891/DK/NIDDK NIH HHS; DK59261/DK/NIDDK NIH HHS; DK70534/DK/NIDDK NIH HHS; P50 HL083801-040003/HL/NHLBI NIH HHS; U54HD41748/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Androgen; 521-18-6/Dihydrotestosterone |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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