CONTROL OF SERTOLI CELL PROLIFERATION

一个独特的系统已经开发出来，用于研究控制因素， 支持细胞成熟数的建立及生长和 睾丸的精子产生。 用这种方法，睾丸大小和精子 成年大鼠的产量可分别增加80%和140%， 用可逆性致甲状腺肿剂短期治疗新生儿 6-丙基-2-硫氧嘧啶（PTU）。 此外，Sertoli细胞数量是 在PTU处理的大鼠中增加了170%。 PTU的机制 治疗增加睾丸生长和精子产生是未知的，但 支持细胞增殖的增加似乎是 这种效应的发展。 本提案中的研究将使用 通过体外和体内方法来确定 PTU治疗增加支持细胞数量，并将测试两个基本的 假设 首先，PTU治疗的大鼠缺乏甲状腺激素， 延迟支持细胞的成熟，使它们保持在一个 幼年期，增殖期较长，处于出生后早期发育阶段。 第二，另一个因素（例如，TSH升高和Sertoli升高 细胞对FSH的反应性）在此期间刺激支持细胞有丝分裂。 出生后增殖期延长，导致成年后 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 特别是增加我们对甲状腺激素作用的理解， 在支持细胞增殖中的作用，并进一步加深了我们对 其调节早期支持细胞增殖和 这些细胞的最终成年数量。 本研究将确定：1）支持细胞增殖是否是 PTU治疗的幅度增加和/或延长; 2）如果TSH可以 在体外对来自处理和/或对照大鼠的Sertoli细胞具有促有丝分裂作用; 3)PTU治疗是否会增加Sertoli的FSH反应性 4）如果PTU治疗改变了与年龄相关的 有丝分裂反应性降低，通常发生在 新生儿期; 5）甲状腺激素是否控制与年龄有关的 新生儿支持细胞的促有丝分裂反应性降低; 6） 对照组和给药组FSH受体表达的可能差异 支持细胞; 7）甲状腺激素受体可能的差异 在对照和处理的Sertoli细胞中的表达; 8） 支持细胞-生殖细胞相互作用对支持细胞增加的影响 在PTU处理的大鼠中观察到增殖。

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.