Pepsinogens: An Update of Biochemical, Physiological, and Clinical Aspects

In this paper the role of pepsinogen has been reviewed in its physiological and clinical aspects. Although acid secretion has traditionally received far more attention clinically and has therefore been studied in great detail, the development of cellular systems has recently seen a revival in interest of pepsinogen secretion. These systems have made it possible to study pepsinogen secretion in more detail. Although many questions remain unanswered, a picture of a stimulus-secretion coupling mechanism of the chief cell has emerged that resembles in many aspects the pancreatic acinar cell, but also possesses some unique features of its own. The chief cell monolayer culture has also made it possible to study pepsinogen synthesis, and these studies seem to have solved the old controversy of whether or not modulation of pepsinogen synthesis occurs as a result of increased secretion. It now seems that pepsinogen synthesis does indeed increase in response to stimulated secretion. In addition to physiological studies, this review has discussed clinical aspects of the human pepsinogens in various gastric disorders. The clinical implications of genetic heterogeneity of the human pepsinogens are especially intriguing. Relationships between certain PGA phenotypes and certain gastric disorders have been described and some studies have tried to evaluate the relevance of these findings for diagnostic purposes. So far, it seems that PGA phenotyping alone has only limited diagnostic value, but, in combination with serum PGA determinations, could be of additional help in the diagnosis of gastric malignancy. In addition, various studies suggest that the ratio of serum PGA and PGC levels may be helpful in determining the histological status of the gastric mucosa. A very promising possibility in solving the many problems involved in exact genotype determinations through phenotyping is the recent availability of cDNA probes. With this technique, the question of whether the association between PGA phenotypes and gastric malignancy is primary or secondary may be solved in the near future. In view of the very poor prognosis for gastric cancer, further studies concerning the relationships between gastric cancer, serum pepsinogen levels, and PGA phenotypes or genotypes will hopefully lead to the possibility of an earlier diagnosis for gastric malignancy.