Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes

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

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

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, PPARγ, leptin, and C/EBPα. 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/EBPα 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.

Original languageEnglish (US)
Pages (from-to)32-40
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume296
Issue number1-2
DOIs
StatePublished - Dec 16 2008

Keywords

  • Androgen
  • Differentiation
  • Preadipocyte
  • Proliferation
  • Testosterone
  • hMSC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes'. Together they form a unique fingerprint.

  • Cite this

    Gupta, V., Bhasin, S., Guo, W., Singh, R., Miki, R., Chauhan, P., Choong, K., Tchkonia, T., Lebrasseur, N. K., Flanagan, J. N., Hamilton, J. A., Viereck, J. C., Narula, N. S., Kirkland, J. L., & Jasuja, R. (2008). Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Molecular and Cellular Endocrinology, 296(1-2), 32-40. https://doi.org/10.1016/j.mce.2008.08.019