Transforming growth factor-alpha and its receptor are expressed in the epithelium of the rat prostate gland.

Abstract

Transforming growth factor-alpha (TGF alpha) is a growth regulatory polypeptide factor that is expressed by several prostatic tumor cell lines. In this investigation, we examined whether TGF alpha is expressed during morphogenesis of the rat prostate gland. We first examined whether the prostate gland expressed TGF alpha by immunohistochemistry. Using a sheep antiserum directed against the mature sequence of TGF alpha, immunoreactivity was identified in the ventral and lateral, but not the dorsal, lobes of the prostate gland from 9-week-old rats. TGF alpha immunoreactivity was localized to a supranuclear site of the epithelial cells, with no immunoreactivity in the stromal cells or elsewhere in the prostate gland. A mouse monoclonal antibody directed against a TGF alpha epitope near cysteine-16 also identified the polypeptide. Furthermore, we confirmed that TGF alpha was synthesized in the epithelial cells of the ventral prostate gland, using an antiserum raised against the intracellular sequences of the transmembrane precursor. To assess the primary target for TGF alpha, we examined expression of receptors for TGF alpha (epidermal growth factor receptor) and found receptors to be localized to the apical surface of the epithelial cells of the ventral prostate gland. We next investigated a potential developmental role for TGF alpha in the rat prostate by examining TGF alpha expression in ventral rat prostate glands ranging from 8 days postpartum to 9 weeks of age. We found that TGF alpha expression was directly proportional to the developmental stage of the gland. Significantly, the fourth week of prostate development marked the appearance of TGF alpha expression in the supranuclear region of the epithelial cells. Immunohistochemical staining of progressively mature prostates of 5 and 6 weeks that contain more complex acinar formations exhibited more intense and highly localized TGF alpha staining. In conclusion, TGF alpha and its receptor have been identified in the apical region of epithelial cells of the rat prostate, and there is reason to believe that TGF alpha may function as an autocrine factor that promotes differentiated functions in the prostate gland.