Binding Energy and the Stimulation of Hormone Receptors

Abstract

To fulfill their physiological roles a hormonal agonist and its receptor must first recognize each other and proceed to a highly specific binding interaction. It is generally believed that this interaction leads to some degree of conformational change in the receptor (receptor stimulation) which in many cases is coupled to an effector system that regulates the intracellular levels of a second messenger such as cyclic AMP or calcium ions. Amplification of the signal arising from the agonist-receptor interaction usually depends upon the initiation of a cascade by the second messenger which culminates in the appropriate biological end response. In other instances the receptor directly controls ion fluxes across the cell membranes (e.g. nicotinic receptors). Steroid receptors after stimulation translocate to the cell nucleus and activate transcription of specific regions of the genome. The amplification systems, which are such a striking feature of hormonal and neuroendocrine action, have been the subject of intense research activity for the past two decades. The situation is very different with regard to the nature of the primary interaction between agonists and their receptors and the conformational changes that ensue. There have been a few reports of efforts to analyze the basic thermodynamics of the binding phenomenon in receptor systems which will be discussed later but little or no effort has been directed to the study of the influence of ligand structure on essential conformational changes in the receptor.