Effect of growth hormone on the differentiation of bovine preadipocytes into adipocytes and the role of the signal transducer and activator of transcription 5b

We evaluated the effect of GH on the differentiation of primary bovine preadipocytes into adipocytes. Bovine preadipocytes, derived from adipose tissue explants, were induced to differentiate into adipocytes in the presence or absence of recombinant bovine GH. The differentiation status of adipocytes was assessed by Oil Red O staining and by measuring the activity of glycerol-3-phosphate dehydrogenase (G3PDH) and the rate of acetate incorporation. Fewer preadipocytes became adipocytes in the presence of GH than in the absence of GH; adipocytes formed in the presence of GH had lower G3PDH activity and lower rate of acetate incorporation than those formed without GH treatment (P < 0.05). These data suggest an inhibitory effect of GH on the differentiation of bovine preadipocytes into adipocytes. Growth hormone decreased the expression of C/EBP alpha and PPAR gamma mRNA in bovine adipocytes (P < 0.05). Because C/EBP alpha and PPAR gamma are the master regulators of adipocyte differentiation, this data suggests that GH might inhibit the differentiation of bovine preadipocytes into adipocytes by inhibiting the expression of C/EBP alpha and/or PPAR gamma. Because the signal transducer and activator of transcription 5 (STAT5) is a major component of signaling from the GH receptor, we next determined the potential role of STAT5 in GH inhibition of bovine adipocyte differentiation. Overexpression of a constitutively active form of STAT5b (STAT5bCA) in bovine preadipocytes through adenoviral transduction mimicked the effects of GH on the formation of lipid-containing adipocytes, G3PDH activity, and acetate incorporation rate. Overexpression of STAT5bCA was associated with decreased expression of C/EBP alpha mRNA (P < 0.05) but not that of PPAR gamma mRNA in bovine adipocytes. These results support a role of STAT5b in mediating GH inhibition of C/EBP alpha expression but not that of PPAR gamma expression in bovine preadipocytes. Overall, the present study suggests that GH may inhibit adipose growth in cattle in part by inhibiting adipogenesis and that GH inhibits the differentiation of bovine preadipocytes to adipocytes through STAT5b-dependent inhibition of C/EBP alpha expression and STAT5b-independent inhibition of PPAR gamma expression.