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ESTROGEN AND REGULATING EFFERENT DUCTS OF TESTIS

雌激素与调节睾丸传出管

基本信息

批准号：
2853751
负责人：
Rex Allen Hess
金额：
$ 1.71万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-11-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/2853751
关键词：
biological fluid transport chloride ion electrophysiology epididymis estrogen inhibitor estrogens gene targeting genetically modified animals hormone regulation /control mechanism laboratory mouse male osmotic pressure potassium ion sodium ion testis

项目摘要

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.

长期目标是了解雌激素作用的机制在男性生殖道和相关的雌激素受体与少精症相关的人类男性不育症的功能障碍，附睾头部精子肉芽肿。雌激素受体α (ER)对男性生殖道的正常生长至关重要， ER基因敲除小鼠（ERKO）中的ER功能障碍导致不育。的 ERKO小鼠的输出管不重吸收液体，这导致液体回流到睾丸，随后诱导睾丸萎缩在人类中，ER-α和P450的突变功能障碍芳香化酶（将雄激素转化为雌激素）计数并导致精子活力差。他莫昔芬，通常已知在不同的环境中是混合的雌激素激动剂/拮抗剂组织，已被临床用于增加精子计数，少精男性拟议中的实验将检验这一假设雌激素刺激输出管中的液体重吸收，改变Cr分泌或Na+转运或两者。具体目标是：a）测量由以下调节的流体重吸收的幅度：正常人附睾输出管和起始段内雌激素水平，抗雌激素处理的和ERKO小鼠; B）测量 Na+，K+，和CI-和渗透压在三个腔液治疗组：和c）将微穿刺数据与 ERKO中NaCl体外吸收的电生理学改变输出导管上皮和经处理的培养导管上皮抗雌激素拟议的研究是根本的了解雌激素和男性不育。