ESTROGEN AND REGULATING EFFERENT DUCTS OF TESTIS

长期目标是了解雌激素的作用机制。 在男性生殖道中的表达与雌激素受体的关系 少精子症与男性不育症相关的功能障碍 附睾头的精子肉芽肿。雌激素受体-α (ER)对男性生殖道的正常生长是必不可少的， ER基因敲除小鼠(ERKO)的内质网功能障碍会导致不孕。这个 ERKO小鼠的传出管道不能重新吸收液体，这会导致 液体回流到睾丸，随后导致睾丸 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)使精子减少。 精子计数和结果显示精子存活率较低。他莫昔芬，这是 通常是一种混合雌激素激动剂/拮抗剂在不同的 组织，已在临床上用于增加精子数量 少精子症的男人。拟议中的实验将检验这一假设。 雌激素通过以下方式刺激传出管内液体的重吸收 改变铬分泌或钠离子转运，或两者兼而有之。具体目标 是：a)测量液体重吸收的大小， 附睾管和附睾段起始部雌激素正常， 抗雌激素治疗的小鼠和ERKO小鼠；b)测量 三组腔液中Na+、K+、CI-和渗透压的变化 治疗组：和c)将显微穿刺术数据与 Erko体外吸收NaCI的电生理改变 传出导管上皮和培养的导管上皮治疗 服用抗雌激素药物。这项拟议的研究是 对雌激素与男性不育的认识。

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.