Tilley W D, Horsfall D J, Skinner J M, Henderson D W, Marshall V R
Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia.
Prostate. 1989;15(2):195-210. doi: 10.1002/pros.2990150213.
Using an immunocytochemical assay (ERICA) with a monoclonal antibody (H222Sp gamma) to the human estrogen receptor, we have demonstrated a stromal localization of the estrogen receptor in the dorsolateral prostate of the guinea pig. Specific staining of estrogen receptor in the guinea pig prostate was confined to the nuclei of periacinar and interacinar stromal cells. In comparison with prepubertal tissues, estrogen receptor staining intensity was markedly reduced in postpubertal prostatic tissues. No immunoreactive estrogen receptor was detected in the acinar epithelial cells irrespective of the developmental stage of the guinea pig prostate. Electron microscopic examination of the guinea pig prostate showed that the stromal component consists predominantly of smooth muscle cells, which, during pubertal development, undergo marked cytological changes and increase in size. These changes in the prostatic stroma were associated with a greater than fivefold reduction in levels of cytosolic and nuclear estrogen receptor determined by either a radioligand binding assay or an enzyme immunoassay (EREIA) and expressed relative to soluble protein. Morphometric analysis of the prostatic stromal cell density (SCD: nuclei/mm2 interacinar stroma), which is inversely proportional to stromal cell size, indicated that the SCD decreased approximately threefold during pubertal development. Furthermore, cytosolic estrogen receptor levels in mechanically separated prostatic stromal fractions were found to vary concordantly with the SCD during pubertal development. To determine whether estrogen influences normal development of the guinea pig prostate, the effect of various hormonal manipulations on stromal development was examined. Castration of prepubertal animals prevented the threefold decrease in SCD that is characteristic of pubertal development. Treatment of prepubertal castrates with estradiol and 5 alpha-dihydrotestosterone (DHT) in combination over a period equivalent to the transpubertal growth phase resulted in a stromal cell density similar to that seen in prostatic sections from intact postpubertal animals. In contrast, treatment of prepubertal castrates with either estradiol or DHT alone resulted in a prostatic stromal cell density intermediate between that observed in intact prepubertal and postpubertal animals. These findings suggest that both estrogen and androgen are required for the normal development of the guinea pig prostatic stroma.
我们使用一种针对人雌激素受体的单克隆抗体(H222Spγ)进行免疫细胞化学分析(ERICA),证实在豚鼠背外侧前列腺中雌激素受体定位于基质。豚鼠前列腺中雌激素受体的特异性染色局限于腺泡周围和腺泡间基质细胞的细胞核。与青春期前组织相比,青春期后前列腺组织中雌激素受体染色强度明显降低。无论豚鼠前列腺处于何种发育阶段,在腺泡上皮细胞中均未检测到免疫反应性雌激素受体。豚鼠前列腺的电子显微镜检查显示,基质成分主要由平滑肌细胞组成,在青春期发育过程中,这些平滑肌细胞会发生明显的细胞学变化并增大。前列腺基质的这些变化与通过放射性配体结合分析或酶免疫分析(EREIA)测定并相对于可溶性蛋白表示的胞质和核雌激素受体水平降低超过五倍相关。前列腺基质细胞密度(SCD:腺泡间基质每平方毫米细胞核数)的形态计量分析表明,在青春期发育过程中SCD下降了约三倍,而SCD与基质细胞大小成反比。此外,发现在青春期发育过程中,机械分离的前列腺基质部分中的胞质雌激素受体水平与SCD一致变化。为了确定雌激素是否影响豚鼠前列腺的正常发育,研究了各种激素处理对基质发育的影响。青春期前动物去势可防止青春期发育特有的SCD下降三倍。在相当于青春期后生长阶段的时间段内,用雌二醇和5α-双氢睾酮(DHT)联合处理青春期前去势动物,导致基质细胞密度与完整青春期后动物前列腺切片中的密度相似。相反,单独用雌二醇或DHT处理青春期前去势动物,导致前列腺基质细胞密度介于完整青春期前和青春期后动物之间。这些发现表明,雌激素和雄激素对于豚鼠前列腺基质的正常发育都是必需的。