CONTROL OF SERTOLI CELL PROLIFERATION

已经开发出一种独特的系统来研究控制因素 成体支持细胞数量的建立及其生长发育 睾丸的精子产生。用这种方法，睾丸大小和精子 成年大鼠的产生量可分别提高80%和140%。 新生儿短期可逆性甲状腺激素治疗 6-丙基-2-硫氧嘧啶(PTU)。此外，支持细胞的数量是 在PTU处理的大鼠中增加了170%。PTU的作用机制 治疗增加睾丸生长和精子产量是未知的，但 Sertoli细胞增殖增加似乎是 这一效应的发展。本提案中的研究将使用 体外和体内方法，以确定其作用机制 PTU治疗增加了支持细胞的数量，并将测试两种基本的 假设。首先，PTU治疗的大鼠缺乏甲状腺激素 延迟Sertoli细胞的成熟，使其保持在 幼体，在出生后发育早期增殖期较长。 第二，另一个因素(S)(例如，TSH和Sertoli增加) 细胞对FSH的反应性)在此过程中刺激支持细胞有丝分裂 出生后增殖期延长，导致成体增加 支持细胞数量，其次是睾丸中观察到的增加 体重和精子产量。这些研究的结果应该是 特别是增加我们对甲状腺激素作用的了解 在支持细胞增殖中的作用和我们对这些因素的进一步了解 它调节早期支持细胞的增殖和建立 这些细胞的最终成体数量。 这项研究将确定：1)支持细胞的增殖是否 PTU治疗后幅度增加和/或延长；2)TSH是否可以 在体外对治疗大鼠和/或对照大鼠的支持细胞有丝分裂作用； 3)PTU治疗是否增加Sertoli对FSH的反应性 4)PTU治疗是否改变了年龄相关的 有丝分裂反应性下降，这通常发生在 新生儿期；5)甲状腺激素是否控制年龄相关 新生儿支持细胞有丝分裂反应性降低；6) 对照组和治疗组FSH受体表达的可能差异 支持细胞；7)甲状腺激素受体的可能差异 在对照和处理的Sertoli细胞中的表达；8) 支持细胞-生殖细胞相互作用导致支持细胞增多 PTU处理的大鼠可见细胞增殖。

A unique system has been developed for studying the factors which control the establishment of the adult number of Sertoli cells and the growth and sperm production of the testis. With this method, testis size and sperm production in adult rats can be increased 80% and 140%, respectively, by a short neonatal treatment with the reversible goitrogen 6-propyl-2-thiouracil (PTU). Furthermore, Sertoli cell numbers are increased by 170% in PTU-treated rats. The mechanisms by which PTU treatment increases testis growth and sperm production are unknown, but increased Sertoli cells proliferation appears to be the critical event in the development of this effect. The studies in this proposal will use both in vitro and in vivo approaches to determine the mechanism by which PTU treatment increases Sertoli cell numbers, and will test two basic hypotheses. First, that the lack of thyroid hormones in PTU-treated rats delays the maturation of Sertoli cells, allowing them to remain in a juvenile, proliferative stage longer during early postnatal development. Second, that another factor(s) (e.g., increased TSH and increased Sertoli cell responsiveness to FSH) stimulates Sertoli cell mitosis during this extended postnatal proliferative period, resulting in the increased adult Sertoli cell numbers and secondarily, the observed increases in testis weight and sperm production. The results of these studies should specifically increase our understanding of the role of thyroid hormones in Sertoli cell proliferation and further our knowledge of the factors which regulate early Sertoli cell proliferation and the establishment of the ultimate adult numbers of these cells. This study will determine: 1) Whether Sertoli cell proliferation is increased in magnitude and/or prolonged by PTU treatment; 2) if TSH can be mitogenic for Sertoli cells from treated and/or control rats in vitro; 3) whether PTU treatment increases the FSH responsiveness of Sertoli cells from treated rats; 4) if PTU treatment alters the age-related decrease in mitogenic responsiveness that normally occurs during the neonatal period; 5) whether thyroid hormones control the age-related decrease in mitogenic responsiveness of neonatal Sertoli cells; 6) possible differences in FSH receptor expression in control and treated Sertoli cells; 7) possible differences in thyroid hormone receptor expression in control and treated Sertoli cells; 8) the importance of Sertoli cell-germ cell interactions for the increased Sertoli cell proliferation seen in PTU-treated rats.