Translational control of hepatic alpha2u globulin synthesis by growth hormone.

α_2u Globulin is a male rat liver protein under complex hormonal control which represents approximately 1% of hepatic protein synthesis in an adult male rat. Hypophysectomy completely abolishes the hepatic synthesis of this protein, and the reinduction of its synthesis can be effected by the simultaneous administration of glucocorticoid, androgen, thyroid hormone and pituitary growth hormone. Growth hormone is absolutely required for the synthesis of a normal level of α_2u globulin. It was found, however, that hepatic α_2u globulin mRNA can be raised to a normal level in hypophysectomized animals by administration of steroids and thyroid hormone alone; nevertheless, no detectable synthesis of the protein occurs in these animals. Administration of growth hormone to the hypophysectomized animals that had been pretreated with steroids and thyroid hormone results in the immediate synthesis of α_2u globulin protein with very little change in the level of α_2u globulin mRNA. In an intact male animal, α_2u globulin mRNA sequences are found to be preferentially associated with bound polysomes. By contrast, the untranslated α_2u globulin mRNA sequences that accumulate in the livers of hypophysectomized rats treated with steroids and thyroid hormone are found on free polysomes and in the supernatant (nonpolysomal) fractions. Administration of growth hormone to these animals effects a shift of α_2u globulin mRNA sequences to bound polysomes, concurrent with the induction of detectable synthesis of the protein. This effect of growth hormone in vivo can be mimicked by administration of high doses of insulin, indicating that this effect may be somatomedin-mediated. It thus appears that growth hormone induces hepatic α_2u globulin synthesis by way of a translational control mechanism.