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The mechanisms whereby growth hormone and dexamethasone modulate the stimulation of fatty acid synthesis by insulin in adipose tissue from lactating and non-lactating sheep have been investigated. Maintenance of adipose tissue from wethers (castrated male sheep) in tissue culture for 24 or 48 h with insulin resulted in an increased proportion of acetyl-CoA carboxylase being present in the active state; this effect was enhanced by dexamethasone and was antagonized by growth hormone. Lactation results in a decrease in both the total acetyl-CoA carboxylase of sheep adipose tissue and the proportion of the enzyme in the active state. Maintenance of adipose tissue from lactating sheep in tissue culture for 48 h in the presence of insulin plus dexamethasone increased markedly the proportion of acetyl-CoA carboxylase in the active state and increased slightly the total activity of the enzyme. Both of these effects were prevented by actinomycin D, and the change in activation status was prevented by growth hormone. Tissue culture for 6 days showed that growth hormone could also prevent the ability of insulin plus dexamethasone to increase the total activity of the enzyme. Analogous studies showed that insulin, dexamethasone and growth hormone modulated the activities of other lipogenic enzymes, but the effects were proportionately smaller than for acetyl-CoA carboxylase. Insulin also increased total protein synthesis in adipose tissue, but this was not antagonized by growth hormone. The results suggest that the fall in fatty acid synthesis in sheep adipose tissue during lactation is due to a decrease in both the total acetyl-CoA carboxylase activity and the proportion of the enzyme in the active state; these changes are probably induced by known changes in the serum concentrations of insulin and growth hormone. Lactation appears to result in the loss of a protein that is required for activation of acetyl-CoA carboxylase by insulin; production of this component appears to be prevented by growth hormone.

biochemical journal

Modulation of the activity of acetyl-CoA carboxylase and other lipogenic enzymes by growth hormone, insulin and dexamethasone in sheep adipose tissue and relationship to adaptations to lactation