GROWTH-HORMONE INHIBITION OF LIPOGENESIS IN SHEEP ADIPOSE-TISSUE - REQUIREMENT FOR GENE-TRANSCRIPTION AND POLYAMINES

The chronic inhibitory effect of growth hormone (GH) on lipogenesis in sheep adipose tissue explants was investigated in an in vitro tissue culture system. In the absence of other hormones, GH caused a decrease in the rate of lipogenesis after 6 h of culture. In contrast, when li pogenesis was stimulated by the presence of insulin plus dexamethasone , GH again decreased Lipogenesis but after a lag of at least 12 h. Act inomycin D, an inhibitor of gene transcription, prevented the effect o f GH on lipogenesis in both the absence and presence of insulin plus d examethasone. Actinomycin D added to tissue previously incubated for 6 h in the presence of GH alone prevented further decline in lipogenesi s over the next 5 h, suggesting that transcription of a short-lived me diator protein is required for the GH effect to occur. An increase in ornithine decarboxylase activity was detected in explants exposed to G H, reaching a peak after 12 h incubation; this was prevented by actino mycin D. Methylglyoxal bis-(guanylhydrazone), an inhibitor of polyamin e biosynthesis, partially alleviated the effect of GH on lipogenesis; this was reversed by addition of spermidine. However, spermidine did n ot reverse the effects of actinomycin D, implicating a short-lived pro tein in addition to ornithine decarboxylase in the action of GH. In th e absence of other hormones GH had no effect on either the expressed ( initial) or total activity of acetyl-CoA carboxylase, but GH prevented the increase in both expressed and total activities of the enzyme ind uced by insulin plus dexamethasone. Varying lipolysis and fatty acid a ccumulation in adipose tissue by addition of adenosine deaminase plus indomethacin or bovine serum albumin to the culture medium had no effe ct on lipogenesis and these agents partly alleviated GH inhibition lip ogenesis. No effect of GH was found on the amount of glycerol released by cultured tissue. GH also had no effect on fatty acid esterificatio n. Thus the chronic inhibitory effects of GH on lipogenesis involve a protein with a very shea half-life. The effect also requires polyamine s but does not appear to involve changes in fatty acid concentrations in the cell. In addition GH appears to inhibit lipogenesis and to anta gonise insulin-stimulation of lipogenesis by different mechanisms.