Estrogen Receptor Heterogeneity and Uterotropic Response

Abstract

For several years investigators have suggested that at least two forms of estrogen binding sites exist in the uterus (Best-Belpomme et al. 1970; Ellis and Ringold 1971 ; Erdos et al. 1969; Michel et al. 1974; Puca et al. 1971 ; Sanborn et al. 1971; Steggles and King 1970). One of these sites, the estrogen receptor, has been intensively investigated (Baulieu et al. 1975; Clark et al. 1978a; Gorski and Gannon 1976; Jensen et al. 1974; O’Malley and Means 1974). This receptor is a protein macromolecule that binds estrogens in a stereospe- cific manner and is found in the cytosol of estrogen-sensitive cells. It has a very high affinity for estradiol (K _d ~ 10^-9 M) and is generally considered to exist in uterine cells at a concentration of about 20,000 sites per cell or ~0.5 pmol/100 μg DNA (Anderson et al. 1972; Clark and Gorski 1969; Katzenellenbogen et al. 1973). The other binding site(s) has received little attention and is often ignored or considered to result from serum albumin or α-fetoprotein (Katzenellenbogen et al. 1973). Early work indicated that dissociation of estrogen from a single binding site could not easily account for this multiplicity, and so two or more sites were proposed (Sanborn et al. 1971; Best-Belpomme et al. 1970; Erdos et al. 1969; Ellis and Ringold 1971; Puca et al. 1971). Rochefort and Baulieu (1969) had noted previously the presence of a secondary site in the uterus that bound estradiol with low affinity but very high capacity.