Differential endocrine regulation of α_2U-globulin messenger ribonucleic acid activity: Effect of age at hypophysectomy

Three α_2u-globulin products were identified on two-dimensional gel electrophoretograms of the [³⁵S]methionine-labeled products formed in response to total hepatic RNA by the reticulocyte lysate translational assay. These products, arbitrarily designated A, B, and C, were quantified by videoimaging of two-dimensional electrophoretograms. At both 65 and 85 days, they represent approximately 13%, 10%, and 77%, respectively, of the total translational products coding for α_2u-globulin. Hypophysectomy at either 30 or 55 days resulted in a marked decrease in all three products when measured at 60 and 85 days. Products A and B were not induced in animals hypophysectomized (hypox) at 30 days and subsequently reinjected for 10 days beginning on day 50 with GH alone; with T₄, corticosterone, and dihydrotestosterone (three hormones); or with a four-hormone combination. Product C was significantly induced by the four-hormone combination. In animals hypox at 55 days and reinjected for 10 days beginning on day 75, GH alone and the three-hormone combination failed to increase product A. In contrast to the observations in animals hypox at 30 days, the four-hormone combination induced a significant increase in products A arid B in animals hypox at 55 days, and product C was induced by the three-hormone as well as the four-hormone combination. Measurement of total α_2u-globulin mRNA by cDNA hybridization indicated that animals hypox at 30 days achieved only 33.8% of age-matched normal levels, whereas animals hypox at 55 days achieved 69% (P < 0.05) when injected with all four hormones. Furthermore, the three-hormone combination increased total α_2u-globulin mRNA in animals hypox at 55 days, but not in animals hypox at 30 days. The observations on the individual α_2u-globulin products suggest that endocrine regulation of individual α_2u sequences is not identical. The different magnitude of response observed in the animals hypox at different ages suggests that exposure of the liver to a pituitarydependent factor between 30 and 55 days modifies the ability of the liver to regulate α_2u-globulin mRNA levels.