Hypophysectomy in mature male rats results in complete abolition of the hepatic synthesis of a2u globulin. Reversal of the effect of hypophysectomy on the synthesis of α2u globulin requires simultaneous treatment with androgen, glucocorticoid, thyroxine, and growth hormone. The mode of action of growth hormone on the hepatic synthesis of α2u globulin was investigated by a correlative study of the hepatic and urinary concentrations of α2u globulin and hepatic concentration of the mRNA for this protein in hypophysectomized rats treated with dihydrotestosterone, corticosterone, and thyroxine and also dihydrotestosterone, corticosterone, thyroxine, and growth hormone. mRNA activity for α2u globulin was quantitated by in vitro translation of the poly(A) containing hepatic RNA in wheat germ cell-free system and subsequent immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the α2u-anti-α2u immunoprecipitate. Results show that inclusion of growth hormone in the three-hormone combination (dihydrotestosterone, corticosterone, and thyroxine) caused more than a sevenfold increase in both hepatic and urinary concentrations of α2u globulin and the hepatic concentration of the mRNA for this protein. The present observation, along with earlier results which have shown that androgen, glucocorticoid, and thyroxine also increase the hepatic concentration of the mRNA for α2u globulin, indicates that the pituitary gland regulates the hepatic synthesis of α2u through a multihormonal regulation of the mRNA for this protein.
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