AGING AND MALE REPRODUCTIVE TRACT STRUCTURE/FUNCTION

衰老与男性生殖道结构/功能

• 批准号: 2001301
• 负责人: BARRY R ZIRKIN
• 金额: $ 78.24万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-12 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2001301
• 关键词: aging; cell age; hormone regulation /control mechanism; male reproductive system; testosterone

Age-related changes in the male reproductive tract are of importance for a number of reasons, including: 1) the population of the U.S. is aging rapidly; 2) a number of diseases of aged men, such as benign prostatic hyperplasia and prostatic cancer, depend upon testicular hormones; 3) other endocrine diseases, such as osteoporosis, are likely to become major problems in geriatric males; 4) aga-related changes in drug and xenobiotic effects have been shown; and 5) couples are waiting until later in life to have children. The male reproductive tract offers many advantages for studies of age-related phenomena, including: 1) experimental manipulation of the tests/epididymides is unlikely to cause death or morbidity; 2) much is known about the regulation of the male tract; and 3) the male reproductive system is an excellent model for generalized aging because it is possible to study, at once, the influence of age on cells that have different proliferative capacities and are at different stages of differentiation. Thus, there are cells that are proliferating rapidly by mitosis (spermatogonia, prostatic epithelia cells), undergoing meiosis (spermatocytes), permanently postreplicative (Sertoli cells), slowly turning over (Leydig cells), differentiating (spermatids), terminally differentiated (spermatozoa), and exquisitely sensitive to hormones and to changes in testicular function (epididymal and prostatic epithelia cells). In the rat, as in the human, striking changes occur with aging, including reduced secretion of testosterone, diminished germ cell production, reduced numbers of testicular and epididymal sperm, atrophy of the seminiferous epithelium, and increased sensitivity of the prostate gland to androgens. The major objectives of this program project application are to elucidate the critical structural and functional changes associated with aging of Leydig (Drs. Zirkin and Wright, Project 1), prostatic (Dr. Brown, Project 2), Sertoli/germ (Drs. Zirkin and Wright, Project 1), spermatozoal (Dr. Robaire, Project 3) and epididymal (Dr. Robaire, Project 3) cells, and to determine the mechanism by which such changes occur.

男性生殖道的年龄相关变化有 重要的原因有几个，包括：1)人口 美国正在迅速老龄化；2)老年男性的一些疾病， 如良性前列腺增生症和前列腺癌 睾丸激素；3)其他内分泌疾病，如 骨质疏松症，很可能成为老年人的主要问题 男性；4)药物和异种生物效应的AgA相关变化 已经被展示过了；而情侣们则等到晚年才会有 孩子们。男性生殖道为 年龄相关现象的研究，包括：1)实验 操纵精液/附睾不太可能导致死亡或 发病率；2)对男性生殖道的调节知之甚多； 3)男性生殖系统是 泛化衰老，因为可以一次研究 年龄对不同增殖能力细胞的影响 处于不同的分化阶段。因此，存在着单元格 通过有丝分裂(精原细胞、前列腺)快速增殖 永久性地进行减数分裂(精母细胞) 复制后(支持细胞)，缓慢翻转(间质细胞)， 分化(精子细胞)、终末分化(精子)、 对荷尔蒙和睾丸的变化非常敏感 功能(附睾腺和前列腺上皮细胞)。在老鼠身上，就像在 随着年龄的增长，人类发生了惊人的变化，包括减少 睾丸激素分泌减少，生殖细胞产量减少 睾丸和附睾精子数量，精子萎缩 生精上皮和前列腺的敏感性增加 腺体对雄激素的作用。该计划项目的主要目标是 应用是为了阐明关键的结构和功能 与Leydig衰老相关的变化(Zirkin和Wright博士， 项目1)、前列腺(Brown博士，项目2)、Sertoli/Germ(Dr. Zirkin和Wright，项目1)，精子(Robaire博士，项目 3)和附睾细胞(Robaire博士，项目3)，并确定 发生这种变化的机制。