Prostaglandins as hormones

Abstract

In recent years, the concept of a hormone has been greatly changed, and the term ‘cybernin’ is used to describe a substance which possesses not only endocrine activity but also has autocrine and paracrine effects. The cytoprotective effects of prostaglandins are reviewed with respect to the relationship between prostaglandins and cyclic AMP, and to the effects of prostaglandins on ion transport. Prostaglandins are produced by cell membranes of many tissues and are found in the vasculature. However, the metabolic degradation of prostaglandins is rapid and their significance as circulatory hormones has not been clarified. Yet it is clear that prostaglandins have important physiological activity and it is possible that the effects of prostaglandins are mediated by paracrine or autocrine mechanisms. In order to classify prostaglandins as hormones, it is necessary to clarify their biological activities, to identify a specific and saturable receptor, and to determine a second messenger. This paper discusses the extent to which prostaglandins conform to our present concept of hormones. The existence of a prostaglandin receptor and the role of adenylate cyclase have been confirmed using cultured cell clones. The following observations have been made. (i) For a series of compounds, potency in competing for (³H)PGE₁ binding sites correlated with their ability to stimulate adenylate cyclase activity. (ii) There was a relationship between rates of binding and change in enzyme activity. (iii) The presence or absence of PGE₁-sensitive adenylate cyclase corresponded to (³H)PGE₁ binding capacity. The presence of a prostaglandin receptor has been identified in rat liver, bovine thyroid, bovine corpus luteum, frog erythrocyte, hamster adipocyte, and human adipocyte. Guanine nucleotides and monovalent cations are also involved. The impact of these studies on our present concept of a hormone's plasma membrane receptor is discussed. There is little information regarding the relationship between Ca⁺⁺ and the effects of prostaglandins on adrenal cortical cells. However, it has been clearly shown that after the administration of prostaglandins in vitro, aldosterone secretion is dependent on Ca⁺⁺, secretion being affected by cyclic AMP concentration, aldosterone concentration, Ca⁺⁺ blockers, and calmodulin inhibitors. These results indicate that prostaglandin receptors are involved. The latest experimental studies concerning the effect of prostaglandins on stomach parietal cells are reviewed.