Anti-oestrophilin antibodies as probes for receptor structure and function

Abstract

The original discovery of steroid hormone receptors (Glascock and Hoekstra, 1959; Jensen and Jacobson, 1960) and essentially all our understanding of hormone-receptor interaction in responsive tissues (Jensen and DeSombre, 1973; Gorski and Gannon, 1976; O’Malley and Schrader, 1976) have depended on experiments in which a radiolabeled hormone serves as a marker for the receptor protein to which it binds. This ligand-binding approach has proved useful in detecting and measuring receptor substances as well as for following the receptor through purification procedures or during its biochemical interaction within the target cell. But despite the wealth of information they have furnished during the past 20 years, ligand-binding procedures suffer from certain limitations. Although strong, the association of hormone with receptor is non-covalent, so the bound steroid is subject to displacement during experimental manipulation of receptor preparations. Furthermore, the receptor proteins are labile substances that irreversibly lose their ability to bind hormone by partial denaturation or by the action of factors present in extracts of many tissues and tumours. Unless some kind of exchange assay is carried out, which usually requires warming, the labelled steroid fails to detect receptor that is already occupied by endogenous hormone. It may also fail to recognise receptor in its early stages of synthesis before it has acquired the ability to bind hormone or in the later stages of its action where the steroid and receptor may have parted company.