Multihormonal control of enzyme clusters in rat liver ontogenesis. II. Role of glucocorticosteroid and thyroid hormone and of glucagon and insulin.

The role of glucocorticosteroid and thyroid hormone and of glucagon and insulin in the pre- and postnatal developmental formation of carbamoyl-phosphate synthase, ornithine transcarbamoylase, arginase, glutamate dehydrogenase, tyrosine aminotransferase, glucose-6-phosphatase, hexokinase and glucokinase activities in rat liver was investigated. Glucocorticosteroids and a low insulin/glucagon ratio always stimulate formation of carbamoyl-phosphate synthase, ornithine transcarbamoylase, arginase, glutamate dehydrogenase, tyrosine aminotransferase and glucose-6-phosphatase, while glucocorticosteroids and a high insulin/glucagon ratio stimulate formation of glucokinase. Thyroid hormone stimulates the formation of carbamoyl-phosphate synthase, arginase and tyrosine aminotransferase only before birth, whereas it stimulates the formation of glutamate dehydrogenase and glucose-6-phosphatase both before and after birth. Ornithine transcarbamoylase activity is depressed after thyroid-hormone treatment before and after birth. DNA content is always decreased by glucocorticosteroids and increased by thyroid hormone. The effect of these hormones on hexokinase is complex, probably due to different responses of the constitutive isozymes. With the exception of the effects of thyroid hormone on carbamoyl-phosphate synthase, arginase and tyrosine aminotransferase before birth, which may be indirect, the responses of enzyme activities and DNA content to treatment with glucocorticosteroid hormones, glucagon, insulin and thyroid hormone are qualitatively the same in fetuses, neonates, sucklings, weanlings and adults. Thus, the developmental profiles of the enzyme clusters reflect the changing levels of the relevant hormones. The enzymes that are stimulated by glucocorticosteroids and the insulin/glucagon ratio show increases in enzyme activity perinatally and around weaning, and relatively low activities in between, while those enzymes that are additionally stimulated by thyroid hormone differ in exhibiting relatively high activities between birth and weaning.