Intermediary Metabolism in the Liver and Adipose Tissue of Rats with Hormone-Secreting Pituitary Tumors

Abstract

Pituitary tumors MtTW5, StW5 and MtTF4, which secrete growth hormone, cause the generalized growth of the host rat, hepatomegalia and depletion of adipose tissue deposits. A prolactin- and ACTH-secreting tumor, 7315a, produced a smaller increase in body growth and hepatomegalia and did not materially deplete the adipose tissue deposits. Adipose tissue from all of these tumor-bearing rats metabolized glucose-1-, or -6-C14 and acetate- 1-C14 to CO2 and fatty acid less well than did tissue from controls. Lipid synthesis was depressed in adipose tissue which had been partially mobilized in vivo (MtTW5 and StW5) and in rats where no mobilization of adipose tissue was observed (7315a). In all hormone-secreting pituitary tumor-bearing rats decreased amounts of glucose were utilized by adipose tissue, but no increase in glycerol release into the medium was observed. Thus, the chronic high levels of growth hormone or prolactin in these rats, resulting in decreased fatty acid biosynthesis, are apparently mediated through a mechanism in addition to inhibition by lipolysis. The activity of the rate-controlling enzyme in fatty acid synthesis, acetyl-CoA carboxylase, was decreased, as was the activity of glucose-6-phosphate and 6-phosphogluconate dehydrogenase in rats with tumors secreting growth hormone. The incorporation of leucine-1-Cl4 into adipose tissue protein was decreased in rats bearing prolactin-secreting pituitary tumors (MtTW5 and 7315a), however, adrenalectomy of rats with 5315a abolished the suppressive effect of the tumor. In contrast to suppressive effects of the pituitary tumor hormones on adipose tissue, these pepetides stimulate the incorporation of acetate-l-Cl4 into fatty acids in the liver. The increase in fatty acid synthesis is directly mediated by the tumor hormones and is not dependent upon the adrenal gland. The rate-limiting enzymes in fatty acid synthesis were increased in the livers of rats bearing growth hormone- and/or prolactin-secreting tumors. The incorporation of leucine-1-C14 into liver protein was increased in tumor-bearing rats. In animals bearing a prolactin-and growth hormone-secreting tumor, protein synthesis was not stimulated in adrenalectomized animals. Liver glycogen concentration was decreased, but, because of the increased liver size, no significant change in the hepatic content was found. An increase in the hepatic RNA/DNA ratio resulted from a small rise in the RNA and a decrease in the DNA concentration. The incorporation of P32 into hepatic phos-pholipid fractions was decreased. Growth hormone and prolactin have anabolic effects in liver and catabolic effects in adipose tissue, but their modes of action are complex.