High-Affinity Binding of Estradiol and Testosterone to Serum Proteins

Abstract

The problem of estrogen binding to serum proteins has been studied intensively by Roberts and Szego (1953, 1955), Szego and Roberts (1953), and Szego (1957). The authors reported initially (Szego and Roberts, 1946; Roberts and Szego, 1946) that twothirds of the total estrogens in human blood was associated with protein, especially with Cohn fraction III-0 containing lipid-poor β₁-globulins of 7 S and 20 S, in addition to β₁-lipoproteins (Cohn, 1947). These early findings, including the estrogens’ capability of dialyzing quantitatively, seemed to suggest a reversible binding system similar to that of other steroid-protein interactions. Later studies in the rat (Szego, 1953, 1955; Szego and Roberts, 1956; Szego, 1960) led to the assumption that the liver was involved in the binding of estrogens to proteins, and an enzymatically catalyzed biosynthesis of “estroprotein” was postulated. Riegel and Mueller (1954) characterized an enzyme system from rat liver which catalyzed the formation of a protein-bound metabolite of estradiol-16-¹⁴C. However, other findings (Bischoff and Stauffer, 1957; Sandberg et al., 1957; Bischoff et al., 1958) did not support the participation of the liver in the origin of the estrogen-protein complexes and assumed albumin to be mainly responsible for estrogen binding in serum. One of the complicating factors in the assumption of liver involvement in the binding of estrogens to protein is the formation of conjugates, especially glucosiduronates (Szego, 1957). These and other metabolites make it difficult to interpret the association of the radiolabeled products with the electrophoretically separated serum protein components (Szego and Roberts, 1956; Szego, 1960).