Febs Letters Volume 85, Number 1-2./Volume 86, Number 1-2. [antikvár]

Volume 85, number 1 FEBS LETTERS January 1978 Review Letter PHYSICAL CHARACTERISATION OF CYTOPLASMIC GLUCO- AND MINERALO- STEROID RECEPTORS M. K. AGARWAL+ INSERM U-36,17Rue du Fer-d-Moulin. Paris 75005, France Received 14 October 1977 1. Introduction Delineation of corticosteroid hormone action is not only one of the few means available to understand the organisation and expression of the complex mammalian genome but it also provides important cues for current therapy in a wide variety of cUnical disorders. The accepted sequence of events is based around the concept where the steroid ligand bound to its cytoplasmic carrier moves into the nucleus and associates itself with the acceptor sites in the target. The present paper is limited to a review of current literature on physical characterisation of the cytosol vector specific for the gluco- and the mineralocorti-coids. This excludes detailed consideration of other steroid binders (viz., albumin, ligandin, transcortin) as well as of receptors for other classes of hormones (estradiol, progesterone, testeosterone) although they have been taken into consideration when relevant. Since a current research on Medlar revealed more than 300 papers during the three preceding years, reference is most often made to a number of existing reviews [1-3] and books [4,5], where possible for both gluco- [1,4,5] andmlneralo- [2-5] groups of hormones. Literature citation is not meant to establish priorities but to lead the reader to an appropriate departing point for further thought. 2. Technical considerations A currently accepted sequence of events in the mechanism of corticoid hormone action consists of ¦•"Mattre de Recherches au CNRS Elsevier/North-Holland Biomedical Press the entry of the lipophilic steroid molecule into the cell cytoplasm with subsequent binding to specific high affinity {K^ 10"'° or close to it), low capacity (therefore saturable) receptors. This complex is thereafter 'activated' by a number of factors (temperature, ionic strength), presumably in the cytoplasm. The activated complex is finally said to penetrate the nuclear membrane and to interact with the acceptor sites in the chromatin and/or DNA as a prerequisite for modulation of the organ specific response. The role of high capacity (thus nonsaturable), low affinity (i^ij approx. 10"') serum binders (transcortin, albumin) is not clear in this sequence of events (discussed later). Thus, a receptor is the immediate requirement for tissue response whereas a binder is an agent capable of transporting the ligand but not necessarily of eliciting the desired reaction. Since the concept of a receptor, by definition, presupposes the presence of a macromolecule within any given target capable of responding to a specific external stimulus by timely, sequential and orderly alteration in a group of processes, a speculative presumption explained corticoid response as a 'one hit' type of mechanism where possibly only one single site may be involved for all grades of agonist and antagonist activity, depending upon the affinity of the ligand for its vector. The ease and rapidity of Scatchard type of analysis further channelled all experimental effort towards the elucidation of a receptor a priori considered homogeneous and unitary by the very nature of definition. More recent comparative work with various techniques based on saturation and competition has revealed discrepancies in the interpretation of results obtained with equilibrium binding, especially since the latter must be disturbed by the addition of 1