Prabagaran Esakki, Hegde Uma C, Moodbidri Sudhir B, Bandivdekar Atmaram H, Raghavan Vijaya P
Department of Biochemistry, National Institute for Research in Reproductive Health (ICMR), J.M. Street, Parel - 400 012, Mumbai, India.
J Androl. 2007 Sep-Oct;28(5):755-71. doi: 10.2164/jandrol.106.002394. Epub 2007 May 9.
The multifunctional and androgen-regulated epididymis is known to provide a conducive microenvironment for the maturation and storage of mature spermatozoa. HOXB2 homeodomain-containing epididymis-specific sperm protein (HOXBES2), a molecule first reported by our group, exhibits cell- and region-specific expression. It was found in the cytoplasm of the principal epithelial cells with maximum in the distal segments of the rat epididymis. The present study was undertaken to determine whether HOXBES2 expression is regulated by androgens and postnatal epididymal development. Toward this, the epididymis was disallowed access to circulating androgens either by chemical or biologic castration. In bilaterally orchidectomized animals, the levels of immunoreactive HOXBES2 declined to <5 % of those seen in sham-operated animals. Exogenous dihydrotestosterone (DHT) supplementation (250 microg/kg body weight) for 7 days restored the expression levels to >or= 90 % of that observed in intact animals. Ethylene dimethane sulfonate (EDS) administration completely abolished HOXBES2 expression in the epididymis, and supplementation with DHT or DHT + estradiol for 10 days re-established HOXBES2 expression to near normalcy. However, in the estradiol alone-supplemented EDS-treated group, HOXBES2 remained undetected. The unaltered HOXBES2 expression following efferent duct ligation suggested that HOXBES2 is not critically dependent on testicular factors. During postnatal development, protein expression in the epididymis begins to appear from day 40 and 50 and increased from day 60 onward, coinciding with the mature levels of circulating androgens and the well-differentiated epididymis. Thus, the data obtained from this study suggests that HOXBES2 expression could be regulated by androgens, and its expression level is closely associated with the postnatal development of the epididymis.
多功能且受雄激素调节的附睾为成熟精子的成熟和储存提供了有利的微环境。含HOXB2同源异型结构域的附睾特异性精子蛋白（HOXBES2）是我们团队首次报道的一种分子，表现出细胞和区域特异性表达。它存在于主上皮细胞的细胞质中，在大鼠附睾远端节段含量最高。本研究旨在确定HOXBES2的表达是否受雄激素和出生后附睾发育的调节。为此，通过化学或生物去势使附睾无法接触循环中的雄激素。在双侧睾丸切除的动物中，免疫反应性HOXBES2的水平降至假手术动物的<5%。补充外源性双氢睾酮（DHT）（250μg/kg体重）7天可将表达水平恢复至完整动物观察值的≥90%。给予乙烯二甲磺酸酯（EDS）可完全消除附睾中HOXBES2的表达，补充DHT或DHT + 雌二醇10天可使HOXBES2表达恢复至接近正常水平。然而，在仅补充雌二醇的EDS处理组中，未检测到HOXBES2。输出小管结扎后HOXBES2表达未改变，提示HOXBES2并非严重依赖睾丸因素。在出生后发育过程中，附睾中的蛋白表达从第40天和第50天开始出现，并从第60天起增加，这与循环雄激素的成熟水平和分化良好的附睾相吻合。因此，本研究获得的数据表明HOXBES2的表达可能受雄激素调节，其表达水平与附睾的出生后发育密切相关。
