Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, India.
Syst Biol Reprod Med. 2010 Dec;56(6):420-30. doi: 10.3109/19396368.2010.501891. Epub 2010 Oct 1.
Modulation of the testis-pituitary axis has direct relevance to the expression of androgen and estrogen receptors. Androgen receptor (AR) and estrogen receptor (ERα) expression during hypospermatogenesis after chronic estrogen administration to rats was studied in the adult testis and pituitary utilizing immunohistochemistry, western blotting, and RT-PCR. Both organs demonstrated higher AR transcriptional activity gradually increasing from 15 days (d) to 30 d of estrogen treatment. However, the AR protein as measured by either immunostaining or western blotting demonstrated a significant decline. A distinct break down of the AR protein in the pituitary into two specific bands was seen. In contrast, higher ERα transcriptional activity coincided well with the rise in protein and immunoexpression in both organs. FSH and testosterone (serum, intra-testicular testosterone) were found significantly (p < 0.001) lowered compared with raised estradiol levels. Spermatogenesis was adversely affected and was associated with a significant increase in cell apoptosis in both organs. The pituitary demonstrated a higher rate of apoptosis at the end of 30 d of estrogen treatment. Taken together, the above data indicate that chronic estrogenization to adult rats up-regulates ERα but down-regulates AR protein expression in testis and pituitary which probably has a direct association to the marked rise in cell apoptosis in these organs.
睾丸-垂体轴的调节与雄激素和雌激素受体的表达直接相关。本研究采用免疫组织化学、Western blot 和 RT-PCR 技术,研究了慢性雌激素处理大鼠后,成年睾丸和垂体中雄激素受体 (AR) 和雌激素受体 (ERα) 在精子发生低下时的表达。两种器官的 AR 转录活性均逐渐升高,从 15 天(d)到 30d 的雌激素处理。然而,AR 蛋白无论是免疫染色还是 Western blot 检测,均显示出明显下降。在垂体中,AR 蛋白明显分解为两个特定的条带。相比之下,ERα 转录活性的升高与两种器官中蛋白和免疫表达的升高相吻合。与升高的雌二醇水平相比,发现 FSH 和睾酮(血清、睾丸内睾酮)显著降低(p<0.001)。精子发生受到不利影响,与两种器官中细胞凋亡的显著增加有关。在 30d 的雌激素处理结束时,垂体表现出更高的凋亡率。综上所述,上述数据表明,慢性雌激素化处理成年大鼠可上调 ERα,但下调睾丸和垂体中的 AR 蛋白表达,这可能与这些器官中细胞凋亡的明显增加有直接关系。