Taylor T B, Ramsdell J S
Marine Biomedical and Environmental Sciences, Medical University of South Carolina, Charleston 29412.
Endocrinology. 1993 Sep;133(3):1306-11. doi: 10.1210/endo.133.3.8103450.
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.
转化生长因子-α（TGFα）是一种生长调节多肽因子，由多种前列腺肿瘤细胞系表达。在本研究中，我们检测了TGFα在大鼠前列腺形态发生过程中是否表达。我们首先通过免疫组织化学检测前列腺是否表达TGFα。使用针对TGFα成熟序列的羊抗血清，在9周龄大鼠前列腺的腹侧叶和外侧叶而非背侧叶中鉴定出免疫反应性。TGFα免疫反应性定位于上皮细胞的核上部位，在基质细胞或前列腺的其他部位未发现免疫反应性。一种针对半胱氨酸-16附近TGFα表位的小鼠单克隆抗体也识别出该多肽。此外，我们使用针对跨膜前体细胞内序列产生的抗血清，证实TGFα是在腹侧前列腺的上皮细胞中合成的。为了评估TGFα的主要靶标，我们检测了TGFα受体（表皮生长因子受体）的表达，发现受体定位于腹侧前列腺上皮细胞的顶端表面。接下来，我们通过检测产后8天至9周龄大鼠腹侧前列腺中TGFα的表达，研究了TGFα在大鼠前列腺中的潜在发育作用。我们发现TGFα的表达与腺体的发育阶段成正比。值得注意的是，前列腺发育的第四周标志着上皮细胞核上区域出现TGFα表达。对5周和6周龄逐渐成熟的前列腺进行免疫组织化学染色，这些前列腺含有更复杂的腺泡结构，显示出更强且高度定位的TGFα染色。总之，已在大鼠前列腺上皮细胞的顶端区域鉴定出TGFα及其受体，并且有理由相信TGFα可能作为一种自分泌因子发挥作用，促进前列腺中的分化功能。
