The Unusual Estrogen-Binding Protein (UEBP) of male rat liver: Structural determinants of ligands

Abstract

The unusual estrogen-binding protein (UEBP) found in a male rat liver is a sex dependent protein which differs from other known receptor and transport proteins by the high lability of its complexes with estradiol (E 2) and also the unique specificity of affinity for hormones. In this work values of relative binding affinity (RBA) of the UEBP for 57 steroids and their analogs were determined. The affinity of steroids was characterised by the amount of the unlabeled compound needed for 50% inhibition of [ 3H]-E 2 binding with the UEBP. A number of derivatives of estrane and androstane possess an ability to interact with this protein, in contrast to the derivatives of pregnane, stilbene and triphenylethane. Characterized by RBA values, natural steroids are found to have the following order: estriol > E 2 > 16α-hydroxyestrone = 2α-hydroxytestosterone > 16-epiestriol > estetrol > 17-epiestriol > 2-methoxyestradiol > 5α-androstane-3α,17β-diol > estrone > testosterone > 2β-hydroxytestosterone > 5α-dihydrotestosterone. Affinity of estrogens and androgens for the UEBP diminishes abruptly after removal of 3- and 17-hydroxy groups, masking of these by ether bonds or changing of 17β-hydroxyl to 17α. All the investigated 17-oxo-C 19-steroids, 5β-derivatives of testosterone, its 6β- and 16α-hydroxy metabolites as well as 5α-androstane-3β,17β-diol and 19-nortestosterone exhibit no essential affinity for the protein. On the basis of the results obtained it is suggested that the binding sites for estrogens and androgens in the UEBP molecule overlap but do not completely coincide.