Shao Ruijin, Ljungström Karin, Weijdegård Birgitta, Egecioglu Emil, Fernandez-Rodriguez Julia, Zhang Fu-Ping, Thurin-Kjellberg Ann, Bergh Christina, Billig Håkan
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, SE-40530 Gothenburg, Sweden.
Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E604-14. doi: 10.1152/ajpendo.00350.2006. Epub 2006 Oct 17.
Female mice lacking AR display alterations in ovarian and uterine function. However, the biology of AR in the fallopian tube is not fully understood. To gain an insight into potential roles of AR in this tissue, we demonstrated that eCG treatment increased AR expression in a time-dependent manner and subsequent treatment with hCG decreased AR expression in mouse fallopian tubes. This expression pattern was positively associated with 17beta-estradiol and testosterone levels in vivo. Immunohistochemical analysis of fallopian tube epithelial cells revealed that nuclear localization of AR increased in parallel with decreased AR in the cytoplasm following eCG treatment. Moreover, we found that treatment with flutamide upregulated AR expression in immature mice in association with a decrease in serum testosterone levels, whereas the same treatment resulted in downregulation of AR expression in gonadotropin-stimulated mice with concomitant decreases in serum 17beta-estradiol concentrations, suggesting that androgen differs from estrogen in the regulation of AR expression. Furthermore, we demonstrated that DES increased both AR protein expression and nuclear location over a 48-h time course. DHT had rapid effects, with induction of AR expression and translocation at 6 h after injection, but unlike DES it had prolonged efficacy. In addition, we provided direct in vivo evidence that nuclear protein interaction between AR and p21(Cip1), a previously reported AR-regulated gene, was enhanced by gonadotropin stimulation. To our knowledge, this study provides the first demonstration to illustrate that estrogen as a principal regulator may contribute to regulate and activate AR in the fallopian tubes in vivo.
缺乏雄激素受体（AR）的雌性小鼠在卵巢和子宫功能方面表现出改变。然而，AR在输卵管中的生物学特性尚未完全了解。为了深入了解AR在该组织中的潜在作用，我们证明了马绒毛膜促性腺激素（eCG）处理以时间依赖性方式增加AR表达，随后用人绒毛膜促性腺激素（hCG）处理可降低小鼠输卵管中的AR表达。这种表达模式与体内17β-雌二醇和睾酮水平呈正相关。对输卵管上皮细胞的免疫组织化学分析显示，eCG处理后，AR的核定位增加，同时细胞质中的AR减少。此外，我们发现氟他胺处理使未成熟小鼠的AR表达上调，同时血清睾酮水平降低，而相同处理导致促性腺激素刺激的小鼠中AR表达下调，同时血清17β-雌二醇浓度降低，这表明雄激素与雌激素在AR表达的调节上有所不同。此外，我们证明己烯雌酚（DES）在48小时的时间进程中增加了AR蛋白表达和核定位。双氢睾酮（DHT）具有快速作用，注射后6小时诱导AR表达和易位，但与DES不同的是，它具有长效作用。此外，我们提供了直接的体内证据，表明促性腺激素刺激增强了AR与p21（Cip1）（一种先前报道的受AR调节的基因）之间的核蛋白相互作用。据我们所知，本研究首次证明雌激素作为主要调节因子可能在体内对输卵管中的AR起到调节和激活作用。
