Banerjee S, Banerjee P P, Zirkin B R, Brown T R
Department of Population Dynamics, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Endocrinology. 1998 Jun;139(6):3005-13. doi: 10.1210/endo.139.6.6060.
The prostate is a highly heterogeneous organ, composed of different types of epithelial and stromal cells organized regionally along the ductal network. Although androgen-stimulated growth and maintenance of the prostate gland primarily involve epithelial cells, it is unclear whether all epithelial cells are androgen dependent. Moreover, the actions of androgens may not be direct; a number of polypeptide growth factors, including transforming growth factor-alpha (TGFalpha), are postulated to mediate androgen action in the rat prostate. In this investigation, using an immunohistochemical technique, we examined the cellular and regional expression of TGFalpha in the rat ventral prostate during postnatal development to adulthood. TGFalpha-immunopositive cells were located throughout the ductal epithelium from postnatal days 5-20. By day 45 and thereafter, regional variation in TGFalpha expression became apparent; epithelial cells in the proximal segment exhibited intense staining, whereas those in the distal segment exhibited negligible staining. These observations were coincident with increased serum testosterone concentrations at puberty. To understand the role of androgen in the expression of TGFalpha in the epithelial cells of the distal and proximal segments of the adult rat ventral prostate, androgen was withdrawn by castration, and testosterone subsequently was administered. Androgen receptor protein expression decreased after castration and reappeared after androgen replacement in both the distal and proximal segments. TGFalpha staining was negligible in epithelial cells of the distal segment of intact adult rats, became prominent by 7 days after castration, but then diminished after the administration of testosterone. Western blot analyses revealed the presence of a specific 30-kDa immunoreactive form of TGFalpha in rat ventral prostate, and its quantity reflected the staining intensities observed in the immunohistochemical studies. These results suggest that TGFalpha expression is negatively regulated by androgen in epithelial cells of the distal segment. In contrast, staining for TGFalpha in epithelial cells of the proximal segment did not change with castration or testosterone administration, suggesting that TGFalpha is not regulated by androgen in this region of the ventral prostate. In summary, TGFalpha expression is differentially regulated among epithelial cells localized in two different regions of the ventral prostate. We hypothesize that TGFalpha may function as a survival factor for epithelial cells which, as a consequence of its expression, become androgen independent and thus escape apoptotic cell death after androgen ablation.
前列腺是一个高度异质性的器官，由沿着导管网络区域组织的不同类型上皮细胞和基质细胞组成。虽然雄激素刺激前列腺的生长和维持主要涉及上皮细胞，但尚不清楚所有上皮细胞是否都依赖雄激素。此外，雄激素的作用可能不是直接的；据推测，包括转化生长因子-α（TGFα）在内的多种多肽生长因子介导雄激素在大鼠前列腺中的作用。在本研究中，我们使用免疫组织化学技术检查了出生后发育至成年期大鼠腹侧前列腺中TGFα的细胞和区域表达。从出生后第5天到第20天，TGFα免疫阳性细胞遍布整个导管上皮。到第45天及之后，TGFα表达的区域差异变得明显；近端段的上皮细胞显示出强烈染色，而远端段的上皮细胞染色可忽略不计。这些观察结果与青春期血清睾酮浓度升高一致。为了解雄激素在成年大鼠腹侧前列腺远端和近端段上皮细胞中TGFα表达中的作用，通过去势去除雄激素，随后给予睾酮。去势后雄激素受体蛋白表达下降，在远端和近端段雄激素替代后重新出现。完整成年大鼠远端段上皮细胞中的TGFα染色可忽略不计，去势后7天变得明显，但在给予睾酮后又减弱。蛋白质印迹分析显示大鼠腹侧前列腺中存在一种特定的30 kDa的TGFα免疫反应形式，其数量反映了免疫组织化学研究中观察到的染色强度。这些结果表明，雄激素对远端段上皮细胞中TGFα的表达具有负调控作用。相反，近端段上皮细胞中TGFα的染色在去势或给予睾酮后没有变化，表明在腹侧前列腺的该区域TGFα不受雄激素调节。总之，TGFα的表达在腹侧前列腺两个不同区域的上皮细胞中受到差异调节。我们假设TGFα可能作为上皮细胞的存活因子，由于其表达，上皮细胞变得不依赖雄激素，从而在雄激素切除后逃避凋亡性细胞死亡。
