Studies on the Mechanism of Diethylstilbestrol-induced Formation of Phosphoprotein in Male Chickens.

The blood of laying hens contains a phosphoprotein fraction that is absent from the blood of nonlaying hens and cockerels (1, 2). This material, like other phosphoproteins (3), carries phosphate on the hydroxyl group of serine (4). Common and his collaborators have isolated phosvitin from the blood of hens that have received estrogen and provided the first evidence for the probable identity of egg and serum phosvitins (5, 6). Heald and McLachlan (7) described a significant chemical similarity between egg phosvitin and phosphoprotein obtained from the blood of untreated, laying hens. In 1945 McDonald and Riddle (8) observed that treatment of male pigeons with est.rogens greatly increases the amount of protein-bound phosphorus in the blood. A report in 1951 provided furt.her evidence for such a response in male fowl: Clegg et al. (9) observed, by electrophoretic analysis, the appearance of a new phosphoprotein in the blood of cockerels a week after the implantation of a diethylstilbestrol pellet. The aim of the present study was to investigate the mechanism whereby such a hormonal stimulus leads to the appearance of a phosphoprotein fraction that is normally undetectable in male chickens. In order to analyze the time sequence of events, prolonged treatment with the hormone was avoided, and conditions were found for studying the effect of a single dose of diethylstilbestrol. Recent studies in this laboratory show (10) that actinomycin, an inhibitor of ribonucleic acid (RNA) synthesis (II), abolishes in viva the rise induced by cortisone in the rat liver of the level of tryptophan pyrrolase and tyrosine-a-ketoglutarate transaminase. These observations indicated that the known stimulation by cortisone of liver RNA synthesis is a necessary part of the enzyme induction process and suggested the hypothesis that regulation of specific protein synthesis by other hormones may also be secondary to a change in RNA metabolism. The present results support this hypothesis and, in addition, define the time period during which RNA metabolism appears to have a critical role. Some of these findings have been reported in a preliminary form (12).