REGULATION OF LEYDIG CELL MITOSIS AND DIFFERENTIATION

拟议的工作将进一步定义控制 间质细胞前体细胞的增殖及向成骨细胞分化 成熟的间质细胞。之前的形态研究由 首席调查员和其他人为 间质细胞分化为间充质样细胞的假说 先祖。在这些研究的同时，间质中的部分 分离未成熟大鼠睾丸细胞，体外培养 进一步明确间质分化的激素要求 来自祖细胞的细胞。这个实验室经常分离出一种 21日龄大鼠睾丸间质细胞组分。那些 仅在体外培养的第3天，细胞显示睾酮的产生增加。 在黄体生成素和黄体生成素联合存在的情况下培养 雄激素。总而言之，结果表明， 间质细胞富含间质细胞祖细胞，而黄体生成素 和雄激素在刺激性激素的转化中起关键作用 祖细胞转化为分泌睾丸激素的间质细胞。研究 这项提案中划定的将实现以下具体目标。在……里面 目的A我们将评估黄体生成素、雄激素和两种激素的各自作用。 生长因子(胰岛素样生长因子-I和白细胞介素1) 祖细胞、未成熟和成体间质细胞的增殖。在……里面 目标B我们将研究这些因素刺激的机制 祖细胞分化为未成熟的间质细胞，以及 未成熟成成年间质细胞。在目标C中，我们将通过以下方式研究这些机制 这些因素调节睾酮生物合成的活性 以及在祖细胞分化为 未成熟的间质细胞和未成熟的成年间质细胞。

The proposed work will further define the mechanisms controlling the proliferation of Leydig cell progenitors and their differentiation into mature Leydig cells. Previous morphological studies carried out by the Principal Investigator and others provide strong support for the hypothesis that the Leydig cell differentiates from a mesenchymal-like progenitor. In parallel with these studies, fractions of interstitial cells from testes of immature rats were isolated and cultured in vitro to further define the hormonal requirements for differentiation of Leydig cells from progenitor cells. This laboratory has routinely isolated a fraction of interstitial cells from the testes of 21-day-old rats. Those cells showed increased production of testosterone on day 3 in vitro only when cultured in the combined presence of luteinizing hormone (LH) and androgen. Taken together, the results indicate that the fraction of interstitial cells was enriched for Leydig cell progenitors, and that LH and androgen have key roles in stimulating the conversion of the progenitor cell into the testosterone-secreting Leydig cell. Studies delineated in this proposal will achieve the following Specific Aims. In Aim A we will evaluate the respective roles of LH, androgen, and two growth factors (insulin-like growth factor-I and interleukin-1) in proliferation of progenitor cells, immature, and adult Leydig cells. In Aim B we will study the mechanisms by which these factors stimulate differentiation of progenitor cells into immature Leydig cells, and immature into adult Leydig cells. In Aim C we will study the mechanisms by which these factors regulate the activities of testosterone biosynthetic and metabolizing enzymes during differentiation of progenitor cells into immature Leydig cells and immature into adult Leydig cells.