Effects of growth hormone on lipogenic enzyme activities in cultured rat hepatocytes.
The presence of cloned methionyl human growth hormone at 1 microgram/ml medium for the final 5 days of a 6-day culture period decreased the activity of malic enzyme (EC 1.1.1.40) 45% from 202 to 112, fatty acid synthetase 52% from 26 to 12, and ATP citrate lyase (EC 4.1.3.8) 20% from 192 to 154 nmol NADPH.min-1.mg-1 supernatant protein in rat hepatocytes maintained in serum-free primary culture. Also, the activity of mitochondrial glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) decreased 52% from 20 to 9 nmol.min-1.mg-1 mitochondrial protein. In the same cells, no changes were observed in the activity of 6-phosphogluconate dehydrogenase (EC 1.1.1.44) and lactate dehydrogenase (EC 1.1.1.27). Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) was increased 2.4-fold from 70 to 183 nmol.min-1.mg-1 protein, indicating the activity of this enzyme was paradoxically increased, whereas other enzymes involved in lipogenesis were decreased. Half-maximal decrease of malic enzyme activity and increase of glucose-6-phosphate dehydrogenase activity occurred at 10 and 3 ng methionyl human growth hormone per milliliter medium, respectively. These values are within the range of normal circulating growth hormone concentrations in the rat. The effects on malic enzyme and glucose-6-phosphate dehydrogenase appeared after 3-day exposure to growth hormone. These findings are consistent with the hypothesis that growth hormone antagonizes the action of agents that stimulate the activity of malic enzyme while concomitantly increasing the extractable activity of glucose-6-phosphate dehydrogenase.
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D064429:Fatty Acid Synthases / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D019382:Human Growth Hormone; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D006728:Hormones; D019382:Human Growth Hormone; D013006:Growth Hormone; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D064429:Fatty Acid Synthases; D001275:ATP Citrate (pro-S)-Lyase