[Current data on the structure-activity relationship of gonadotropins].

Most of the available information on the structure-function of gonadotropins is critical for the development of both therapeutic approaches to reproductive malfunctions and new strategies for the control of fertility. Major advances in our understanding of the structure of these hormones and the manner in which they interact with their receptors have been made in recent years. Furthermore, the recent availability of highly purified hormones and their recombinant counterparts as well as the cloning of he receptors offer new tools for the investigation of structure-activity relationship of gonadotropins. The present article reviews: (i) the overall structure of these complex glycoprotein hormones assembled from two distinct alpha (alpha) and beta (beta) subunits, (ii) their heterogeneities in term of carbohydrate and peptidic structures, which influence both the bioactivity and the immunoreactivity of the hormones, (iii) the structure and the functional domains of their receptors, belonging to the G-protein coupled receptor family, and (iv) the more recent information available on the regions of interaction between the subunits and between the hormone and its corresponding receptor. Pioneering work on the topographical features of gonadotropins has been accomplished in a piecemeal fashion by using classic chemical methods of protein modification. In the last ten years, new approaches, including the production of monoclonal antibodies, the construction of synthetic peptides and the use of recombinant DNA technology, provided important insights in the knowledge of these molecules. However, significant progress remains to be accomplished, particularly in the establishment of the three-dimensional structure of these hormones, which are critical for the understanding of pathophysiological processes related to endocrinology and for the design of new peptidic or nonpeptidic analogs useful of therapeutic approaches.