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This Article Full Text Full Text (PDF) All Versions of this Article: jas.2008-1645v1 87/12/3897    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chung, K. Y. Articles by Johnson, B. J. PubMed PubMed Citation Articles by Chung, K. Y. Articles by Johnson, B. J.

Melengestrol acetate enhances adipogenic gene expression in cultured muscle-derived cells

Department of Animal and Food Science, Texas Tech University, Lubbock 79409

¹ Corresponding author: kiyong.chung{at}ttu.edu

Melengestrol acetate (MGA) has been used in the United States for nearly 40 yr to enhance feedlot heifer performance, yet unequivocal studies have not been conducted to discover the mechanism of action. Our hypothesis was that MGA may induce various populations of muscle-derived cells (MDC) to the adipogenic pathway in both a bovine and murine cell culture model. To determine this, MDC were digested from the semimembranosus muscle tissue of six 14-mo-old crossbred steers. The addition of insulin, oleic acid, and ciglitizone (IOC) with cultured bovine MDC resulted in morphological differences compared with control cultures. Multilocular lipid droplets stained with Oil Red O were seen not only in single MDC, but also in fused myotubes. An increase (P < 0.05) in relative PPAR messenger RNA (mRNA) levels was measured in MDC incubated with IOC. However, myogenin mRNA levels in MDC incubated with IOC were repressed (P < 0.05) compared with nontreated MDC. Cultures of MDC treated with 10 µM insulin, 10 µM oleic acid, 10 µM ciglitizone, 10 nM estradiol-17β (E₂), and 10 nM MGA resulted in cultures with highly distributed lipid droplets not only in single cells, but also in the multinucleated myotubes. Relative C/EBPβ and PPAR mRNA levels in total RNA isolated from MDC treated with MGA increased (P < 0.05) compared with control cultures. Estradiol treatment had no effect (P > 0.05) on these mRNA levels. The addition of both E₂ and MGA to MDC increased (P < 0.05) C/EBPβ mRNA levels and tended (P = 0.06) to increase the PPAR mRNA level. There was no difference (P > 0.10) in relative myogenin mRNA among the control, E₂, and MGA treatments. Relative C/EBPβ, PPAR, and myogenin mRNA levels were investigated in murine C2C12, C3H 10T 1/2, and 3T3-L1 cells. Treatment of cultures with 10 nM MGA increased C/EBPβ levels (P < 0.05) in C2C12 myoblasts and tended (P = 0.08) to increase C/EBPβ levels in 3T3-L1 preadipocytes. These data indicate that populations of cells are present in postnatal skeletal muscle that, under the appropriate stimuli in a culture model, express adipogenic genes and accumulate lipids. In addition, the synthetic progestogen MGA appeared to upregulate the genes necessary for conversion to the adipogenic pathway.

Key Words: melengestrol acetate • muscle-derived cell • transdifferentiation