Oxytocin in the human--regulation of derivations and destinations.

Those of us who study physiology are tempted to hope that the experimental perturbations which we induce affect only the organ which has ensnared our interest. This review uses physiological systems which incorporate oxytocin as models to indicate some of the ways in which departure from such investigative paradise occurs, and also to discuss some of the implications of a physiology which uses one compound in several distinct roles. The dual activities of oxytocin, on the uterus and on the mammary gland, for some time constituted the complete portfolio of the peptide’s functions in biology (1). However, now no longer is consideration of oxytocin confined to its two traditional roles. Investigations of oxytocin have demonstrated that oxytocin participates in a wide variety of activities in dispersed regions of the body, and is an element of the physiology of both sexes. Oxytocin is involved with sex, pain and moods, and its sites of action include the thymus, the ovary, and the pancreas. After the oxytocic activity and the milk ejecting activity of the posterior pituitary gland were recognised, a nonapeptide was found to be responsible for the effects. The structure of the compound was established (2, 3) and oxytocin was the first peptide hormone to be purified and synthesised, and available for pharmacologically defined studies. Modern molecular biology has provided information of the oxytocin system (Fig. 1). The oxytocin gene has been mapped to 20p13 (4) although the nature of the regulatory elements critical to cell-specific expression of the oxytocin gene are still ill-defined (5). The molecular structure of the oxytocin receptor has been characterised (6) and the gene has been localised to 3p25–3p26 (7–9). It is assumed that oxytocin has evolved by duplication of an ancestor gene which oxytocin and vasopressin have in common. The vasopressin/oxytocin prohormone ancestor was present in Archaemetazoa, from which vertebrates and invertebrates diverged 600 million years ago (10, 11). This review is designed first to serve as a reminder that a compound can affect multiple entities, secondly to consider some of the processes which control interaction between physiological units, and thirdly to point to the multifaceted effects, including alterations of behaviour, a pathological change can have. A variety of control mechanisms which are incorporated into oxytocin systems are summarised in Table 1 and corresponding examples indicated in the text by upper case letters (A–O). This review considers effects induced by oxytocin which have been observed in human studies, which after all is the ultimate target of most projects, with only occasional reference to antecedent animal investigations. Although animal studies have suggested several activities for oxytocin which are not discussed in this review it is necessary to note that there are some functions of oxytocin which are species specific. Examples are the apparently opposite effects of oxytocin on adrenocorticotrophin (ACTH) in humans (in which oxytocin is reported to be inhibitory) and in rats (in which oxytocin is stimulatory); another is the differences in the temporal profile of oxytocin in the cerebrospinal fluid (CSF) of humans and rats; a third is the distribution of oxytocin binding sites in the brain.