EFFECTS OF AGING ON SERTOLI CELL FUNCTION

衰老对支持细胞功能的影响

• 批准号: 5204601
• 负责人: WILLIAM W WRIGHT
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5204601
• 关键词: Sertoli cells; aging; androgen binding protein; animal old age; cell cell interaction; cell population study; developmental genetics; endocrine pharmacology; epidermal growth factor; estradiol; follicle stimulating hormone; gene expression; germ cells; hormone regulation /control mechanism; in situ hybridization; insulin; laboratory rat; mature animal; messenger RNA; northern blottings; sulfated glycoprotein 2; testis; testosterone; tissue /cell culture; transferrin

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.

棕色挪威大鼠的生精上皮逐渐失去胚芽 随着动物从12个月到24个月的年龄增长， 这一损失 在没有疾病的情况下发生，生殖道阻塞 或血清FSH或睾丸内睾酮的实质性变化 浓度的 然而，伴随着宝石细胞的损失是特定的， 体细胞支持细胞基因表达的变化。 虽然睾丸 SGP-2 mRNA的含量在6-24月龄之间是恒定的， 转铁蛋白mRNA增加。 因此，睾丸老化可能导致 部分来自支持细胞固有的变化。 本提案探讨了这一点 通过检查老化对Sertoli反应的影响， 细胞到生殖细胞和激素。 此外，我们还将探讨 可以防止支持细胞功能的老化相关丧失。 这些 在三个具体目标中阐述了这些目标。 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-2 mRNA的阶段特异性表达是否在 老化，并确定老化是否会降低生殖细胞的能力， 改变体外支持细胞的基因表达。 第二，我们检查 衰老是否会改变体外支持细胞对FSH的反应性， 胰岛素和EGF，所有未成熟或成熟的功能调节剂 支持细胞。 第三，我们确定年龄相关的变化是否 支持细胞功能可以通过改变内分泌状态来预防 衰老的动物。