Immunohistochemical localization of alpha- and betaA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system.

Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one alpha-subunit and one betaA-subunit (alpha-betaA), while activin A is a homodimer of the betaA-subunit (betaA-betaA). Their identification in several tissues has suggested that they have numerous physiological functions, acting as either paracrine or autocrine factors. The aim of this study was to evaluate the expression of activin A and inhibin A in normal endocrine cells and in 70 endocrine tumours from different sites in the gastro-entero-pancreatic system, using specific monoclonal antibodies directed against the alpha- and betaA-subunits of inhibin/activin. Immunoreactivity for the betaA-subunit, but not for the alpha-subunit, was observed in normal G, EC, and GIP cells of the antrum and duodenum, and in pancreatic A cells. BetaA-subunit expression was observed in G cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids. The alpha-subunit was found in rare cells in 7 of the 70 tumours and was colocalized with the betaA-subunit in only 1 tumor. Specific types of endocrine cells from the gut and pancreas appear to produce only activin A, a possible paracrine or autocrine modulator. Activin A is mainly produced by tumours derived from endocrine cells that normally express it.