EFFECTS OF AGING ON SERTOLI CELL FUNCTION

棕色挪威鼠生精上皮逐渐松解 随着动物从12个月龄到24个月龄的增长。这一损失 在没有疾病、生殖道阻塞的情况下发生 或血清卵泡刺激素或睾丸内睾酮的实质性变化 浓度。然而，伴随着GEM细胞丢失的是特定的 体细胞支持细胞基因表达的变化。而睾丸 SGP-2mRNA的含量在6-24月龄期间保持不变，睾丸内容物 转铁蛋白基因表达增加。因此，睾丸老化可能会导致 部分是由于支持细胞固有的变化。这份提案探讨了这一点 通过研究衰老对Sertoli反应的影响提出 从细胞到生殖细胞再到激素。此外，我们还探讨了 可以防止与衰老相关的支持细胞功能丧失。这些 目标分为三个具体目标。首先，我们检查 衰老对生殖细胞-支持细胞相互作用的影响。我们探索 CP-2mRNA的阶段特异性表达是否在 衰老并确定衰老是否会降低生殖细胞的能力 改变支持细胞在体外的基因表达。第二，我们检查 衰老是否会改变体外培养的支持细胞对FSH的反应 胰岛素和EGF，都是未成熟或成熟功能的调节剂 支持细胞。第三，我们确定与年龄相关的变化是否 通过改变内分泌状态可以阻止支持细胞的功能 衰老的动物。

The seminiferous epithelium of the Brown Norway rat gradually looses germ cells as the animals advance from 12 to 24 months of age. This loss occurs in the absence of disease, obstruction of the reproductive tract or substantial changes in serum FSH or intratesticular testosterone concentrations. However, concomitant with loss of gem cells are specific changes in gene expression by the somatic Sertoli cells. While testis content of SGP-2 mRNA is constant from 6-24 months, testis content of transferrin mRNA increases. Testicular aging may therefore result in part from changes inherent to Sertoli cells. This proposal explores this proposition by examining the effect of aging on the responses of Sertoli cells to germ cells and to hormones. Additionally, we explore whether aging-related loss of Sertoli cell function can be prevented. These objectives are addressed in 3 specific aims. First, we examine the effects of aging on germ cell-Sertoli cell interactions. We explore whether the stage-specific expression of CP-2 mRNA is degraded during aging and determine whether aging reduces the capacity of germ cells to alter gene expression of Sertoli cells in vitro. Second, we examine whether aging alters the responsiveness of Sertoli cells in vitro to FSH, insulin and EGF, all modulators of the function of immature or mature Sertoli cells. Third, we determine whether age-related changes in Sertoli cell function can be prevented by altering the endocrine status of the aging animal.