Effect of hypophysectomy on the synthesis of rat liver albumin.

Hypophysectomy of adult rats results in approximately a 50% decrease in the rate of albumin synthesis relative to total liver protein synthesis. This decrease is accompanied by a proportional decline in the number of albumin-synthesizing polysomes, as determined by the binding of 125I-Labeled anti-albumin antibody, and indirect immunoprecipitation of [3H]leucine-labeled albumin-synthesizing polysomes. Furthermore, this decrease is associated with an equivalent reduction in the amount of total membrane-bound polysomes, whereas total free polysomes show little quantitative change. The size of the specific albumin-synthesizing polysomes, as well as the size of the total polysomes, however, appear to be the same following hypophysectomy as in the normal untreated animal. These observations are consistent with the finding that the relative amount of albumin mRNA activity also decreases approximately 50%, as assayed in a heterologous cell-free protein-synthesizing system using exogenous liver RNA prepared from either isolated polysomes or total liver homogenates. The decrease in albumin production in the hypophysectomized rat, therefore, is apparently the result of a reduction in the amount of active albumin mRNA. The concomitant decrease in albumin-synthesizing polysomes appears to reflect a similar reduction in the amount of total membrane bound polysomes. Thus, a major physiological defect in hypophysectomy may be a preferential decline in membrane-bount polysomes accompanied by a reduction in mRNA levels, which is represented by the decrease in albumin synthesis.