Endocrine Abstracts

Although scientists have been seeking the mechanism of action of hormones for over 100 years, which is often before the identity and structures of many hormones were known, we are still unable to say definitively in molecular or structural terms how any hormone exerts a given physiological action. This failure is largely due to the fact that most investigations are technology driven and not hypothesis based. At the same time, two important features of hormones and their actions, namely evolutionary and historical, have often been ignored. Most hormones have been structurally highly conserved during evolution, yet their physiological actions vary enormously in different organisms or from one tissue to another in the same species. Thanks to the rapid advances in technologies based on gene cloning and DNA sequencing in the last 30 years, we know much about receptors, which are a key element of hormone action. Most hormone receptors are located in the cell membrane or nucleus and are cellular homologues of the oncogenes c-erbB or c-erbA. These studies, have established that receptors are highly conserved through evolution, but, again, they do not explain the widely different physiological actions of a given hormone. A historical overview based on a time-line of the progression of new technologies over the last 80 years – from physiological models to biochemical interactions to molecular and structural biology – reveals that our explanations of hormone action are derivatives of newly evolving techniques. We are now at a stage where focusing on immediate post-receptor events in the hormonal target cell might well bring us closer to understanding how any individual hormone brings about a particular physiological action.