Production of activin A in hyperplasia and adenocarcinoma of the human endometrium

Objectives. To examine the possible localization and production of activin A in human normal endometrium, endometrial hyperplasia, and adenocarcinoma tissues. Methods. Human endometrial tissues were collected from 45 patients who were undergoing abdominal hysterectomy. Tissue sections were stained with monoc lonal antibodies against the inhibin/activin alpha- and betaA-subunits and activin A using an avidin-biotin-peroxidase complex technique. Concentratio ns of activin A and inhibin A in tissue extracts of the endometrial tissues were measured using enzyme-linked immunosorbent assays (ELISAs). The expre ssions of the inhibin alpha -subunit and activin betaA-subunit messenger RN A (mRNA) in the endometrial tissues were demonstrated by reverse transcript ion-polymerase chain reaction (RT-PCR) analysis. Results. No immunostaining with an antibody against the inhibin alpha -subu nit was observed in human normal endometrium, endometrial hyperplasia, and adenocarcinoma. By contrast, immunostaining for the activin betaA-subunit a nd activin A was observed in the cytoplasm of glandular cells in normal end ometrium, endometrial hyperplasia, and tumor cells of endometrial adenocarc inoma. The percentages of stained cells in endometrial adenocarcinoma were higher than those in normal endometrium. Also, the percentages of stained t umor cells with poor differentiation were higher than those with good and m oderate differentiation of the endometrium. The stromal cells in normal end ometrium, endometrial hyperplasia, and adenocarcinoma were weakly immunorea ctive with antibodies against the betaA-subunit and activin A. Immunoreacti vity of activin A in tissue extracts from normal endometrium and endometria l adenocarcinoma was detected by the two-site ELISA. Immunoreactivity of ac tivin A was significantly higher in adenocarcinoma than in normal endometri um. On the other hand, the immunoreactive inhibin A was not detected. The e xpression of the alpha -subunit mRNA in endometrial tissues was demonstrate d as the RT-PCR products migrated at 905 bp and the products of the betaA-s ubunit showed a band at 366 bp. Conclusions. It is suggested that activin A, but not inhibins, are produced by endometrial tissues. The amounts of produced activin A were higher in a denocarcinoma tissues than in normal endometrium. Activin A might be involv ed in human endometrial tumorigenesis. (C) 2001 Academic Press.