ESTROGEN AND REGULATING EFFERENT DUCTS OF TESTIS

长期目标是了解雌激素的作用机制 在男性生殖道中并与雌激素受体相关 与少精症相关的人类男性不育功能障碍和 附睾头部的精子肉芽肿。雌激素受体-α (ER) 对于男性生殖道的正常生长至关重要 ER 基因敲除小鼠 (ERKO) 的 ER 功能障碍会导致不孕。 的 ERKO 小鼠的传出管不会重新吸收液体，这会导致 液体回流到睾丸并随后诱导睾丸 萎缩。 在人类中，ER-α 和 P450 突变功能障碍 芳香酶（将雄激素转化为雌激素）减少精子数量 计数并导致精子活力较差。 他莫昔芬，它是 通常被称为混合雌激素激动剂/拮抗剂 组织，已在临床上用于增加精子数量 少精症男性。 所提出的实验将检验假设 雌激素通过以下方式刺激传出管中的液体重吸收 改变 Cr 分泌或 Na 运输或两者。 具体目标 是：a）测量液体重吸收的大小 正常情况下，传出管和附睾起始段中存在雌激素， 抗雌激素治疗小鼠和 ERKO 小鼠； b) 测量浓度 Na 、 K 和 CI- 以及三者腔内液体的渗透压 治疗组：和 c) 比较微穿刺数据 ERKO 体外 NaCl 吸收的电生理变化 传出导管上皮和经过处理的培养导管上皮 与抗雌激素。 拟议的研究对于 了解雌激素和男性不育症。

The long-term objective is to understand mechanisms of estrogen action in the male reproductive tract and to relate estrogen receptor dysfunction to human male infertility associated with oligospermia and sperm granulomas in the head of the epididymis. Estrogen receptor-alpha (ER) is essential for normal growth of the male reproductive tract and ER dysfunction in the ER knockout mouse (ERKO) causes infertility. The efferent ducts of the ERKO mouse do not reabsorb fluid, which causes fluid to back up into the testis and subsequently induces testicular atrophy. In human, mutational dysfunction in ER-alpha and P450 aromatase (which converts and androgens to estrogens) decreases sperm counts and results in poor sperm viability. Tamoxifen, which is commonly known to be a mixed estrogen agonist/antagonist in different tissues, has been used clinically to increase sperm counts in oligospermic men. The proposed experiments will test the hypothesis that estrogen stimulates fluid reabsorption in efferent ducts by altering either Cr secretion or Na+ transport or both. Specific aims are: a) to measure the magnitude of fluid reabsorption regulated by estrogen in efferent ducts and initial segment epididymidis in normal, antiestrogen-treated and ERKO mice; b) to measure the concentrations of Na+, K+, and CI- and osmotic pressure in luminal fluids in the three treatment groups: and c) to compare micropuncture data with electrophysiological alterations in NaCI absorption in vitro in the ERKO efferent ductal epithelium and in cultured ductal epithelium treated with the antiestorgen. The proposed research is fundamental to the understanding of estrogen and male infertility.