Fisher J S, Turner K J, Fraser H M, Saunders P T, Brown D, Sharpe R M
Medical Research Council Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, Scotland, United Kingdom.
Endocrinology. 1998 Sep;139(9):3935-45. doi: 10.1210/endo.139.9.6213.
Recent data suggest that estrogens play a role in regulating fluid resorption from the efferent ducts, though the biochemical mechanisms involved are unknown. The present study has used immunocytochemistry to localize a water channel protein, Aquaporin-1 (AQP-1), to the efferent ducts of male rats and marmoset monkeys from perinatal life through to adulthood and has then investigated its potential hormonal regulation in neonatal/peripubertal life, via administration of a GnRH antagonist (GnRHa) or diethylstilbestrol (DES) to rats. AQP-1 was immunoexpressed intensely in the apical brush border of the epithelium lining the efferent ducts at all ages studied, from late fetal life through puberty to adulthood. In the marmoset, but not the rat, AQP-1 was also expressed in the epithelium of the rete testis. Once the cell types within the efferent duct epithelium had differentiated, it was clear that only nonciliated cells of the rat localized AQP-1. When gonadotropin secretion was suppressed in rats by neonatal administration of GnRHa, immunoexpression of AQP-1 at age 18 and 25 days was virtually unchanged in intensity, though the efferent ducts were reduced in size. In contrast, when DES was administered neonatally to rats (up to day 12), immunoexpression of AQP-1 was reduced at day 10, virtually abolished at day 18, reduced markedly at day 25 and to a small extent at day 35; these findings were confirmed by Western blot analysis at day 18. The DES-induced decrease in immunoexpression of AQP-1 was accompanied by pronounced distension of the efferent ducts and rete, consistent with reduced fluid resorption. The epithelial cells of the efferent ducts in DES-treated rats were cuboidal rather than columnar in shape as in controls and were reduced significantly in height compared with controls at all ages through to adulthood. These findings suggest that estrogens may play a role in regulating fluid resorption from the efferent ducts during fetal/neonatal development and/or a role in the gross and functional development of the efferent ducts and rete testis. The present data also suggest that AQP-1 is one of the elements involved in the regulation of fluid resorption in the efferent ducts. The importance of fluid flow in fetal/neonatal development of the excurrent duct system of the male is also suggested by these observations.
近期数据表明,雌激素在调节输出小管的液体重吸收中发挥作用,尽管其中涉及的生化机制尚不清楚。本研究采用免疫细胞化学方法,将一种水通道蛋白水通道蛋白-1(AQP-1)定位到从围产期直至成年期的雄性大鼠和狨猴的输出小管,并通过给大鼠注射促性腺激素释放激素拮抗剂(GnRHa)或己烯雌酚(DES),研究其在新生儿/青春期前生活中的潜在激素调节作用。在从胎儿晚期到青春期再到成年期的所有研究年龄段中,AQP-1在输出小管内衬上皮的顶端刷状缘中强烈免疫表达。在狨猴而非大鼠中,AQP-1也在睾丸网的上皮中表达。一旦输出小管上皮内的细胞类型分化,很明显大鼠中只有非纤毛细胞定位有AQP-1。当通过新生儿期注射GnRHa抑制大鼠的促性腺激素分泌时,18天和25天时AQP-1的免疫表达强度实际上没有变化,尽管输出小管尺寸减小。相比之下,当在新生大鼠中(直至第12天)给予DES时,10天时AQP-1的免疫表达降低,18天时几乎消失,25天时显著降低,35天时略有降低;这些发现通过18天时的蛋白质免疫印迹分析得到证实。DES诱导的AQP-1免疫表达降低伴随着输出小管和睾丸网的明显扩张,这与液体重吸收减少一致。与对照组相比,DES处理的大鼠输出小管的上皮细胞在所有年龄段直至成年期均呈立方形而非柱状,且高度显著降低。这些发现表明,雌激素可能在胎儿/新生儿发育期间调节输出小管的液体重吸收中发挥作用,和/或在输出小管和睾丸网的大体及功能发育中发挥作用。目前的数据还表明,AQP-1是参与调节输出小管液体重吸收的因素之一。这些观察结果还表明了液体流动在雄性外排管道系统胎儿/新生儿发育中的重要性。