The role of growth hormone in alpha 2u globulin synthesis: a reexamination

Hypophysectomy of adult male rats abolishes alpha 2u globulin synthesis; synthesis can be fully restored by daily administration of androgen, thyroid hormone, glucocorticoid and growth hormone for 12 days. It has been previously reported that growth hormone is not required to maintain alpha 2u globulin mRNA levels, and that growth hormone functions only translationally. We have reexamined the role of growth hormone in alpha 2u globulin synthesis using a cloned alpha 2u globulin cDNA probe. Measurement of alpha 2u globulin mRNA levels by hybridization and cell-free translation, and of alpha 2u globulin synthesis by pulse-labeling in vivo, demonstrates that growth hormone is required to maintain full, steady state hepatic levels of both alpha 2u globulin and its mRNA. Furthermore, the small amount of hepatic alpha 2u globulin mRNA that accumulates in the absence of growth hormone is efficiently translated in vivo. Thus we now find no evidence for growth-hormone-mediated translational control. We have also found that rats hypophysectomized prepubescently respond to the multihormonal restoration therapy to only 10% of the alpha 2u globulin mRNA levels observed in rats hypophysectomized as adults. This finding suggests that some unidentified pituitary factor(s) is required during puberty to potentiate normal alpha 2u globulin gene expression.