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 lipogenesis was stimulated by the presence of insulin plus dexamethasone, GH again decreased lipogenesis but after a lag of at least 12 h. Actinomycin D, an inhibitor of gene transcription, prevented the effect of GH on lipogenesis in both the absence and presence of insulin plus dexamethasone. Actinomycin D added to tissue previously incubated for 6 h in the presence of GH alone prevented further decline in lipogenesis over the next 5 h, suggesting that transcription of a short-lived mediator protein is required for the GH effect to occur. An increase in ornithine decarboxylase activity was detected in explants exposed to GH, reaching a peak after 12 h incubation; this was prevented by actinomycin D. Methylglyoxal bis-(guanylhydrazone), an inhibitor of polyamine biosynthesis, partially alleviated the effect of GH on lipogenesis; this was reversed by addition of spermidine. However, spermidine did not reverse the effects of actinomycin D, implicating a short-lived protein in addition to ornithine decarboxylase in the action of GH. In the 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 induced by insulin plus dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
Borland
C A
CA
Hannah Research Institute, Ayr, UK.
Barber
M C
MC
Travers
M T
MT
Vernon
R G
RG
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D046508:Culture Techniques; D003609:Dactinomycin / Q000494:pharmacology; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008935:Mitoguazone / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D012756:Sheep / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D003609:Dactinomycin; D003907:Dexamethasone; D013006:Growth Hormone; D009955:Ornithine Decarboxylase; D000103:Acetyl-CoA Carboxylase; D008935:Mitoguazone; D013095:Spermidine