男性衰老伴随着广泛的症状,包括性功能障碍,认知和肌肉骨骼衰退,肥胖,2型糖尿病,心血管疾病和高血压,器官退化/衰竭,增加瘤形成,其中一些与Leydig细胞产生的睾酮水平下降有关。高自然生物变异,以及可以调节循环睾酮浓度的多种因素,可能会影响其解释和临床意义。胰岛素样肽3是Leydig细胞功能的生物标志物,可能提供有关睾丸健康及其下游结果的补充信息。
将胰岛素样肽3表征为评估老年男性性腺状态的生物标志物。
分析了一个大型的欧洲多中心(欧洲男性衰老研究)社区居住男性队列,以确定胰岛素样肽3与一系列激素的关系。人体测量学,和生活方式参数。
胰岛素样肽3在个体中的横向和纵向下降,从40岁开始,每十年下降约15%。与睾丸激素(每十年1.9%)不同,部分通过增加垂体促黄体生成激素来补偿。重要的是,较年轻男性中胰岛素样肽3的降低似乎随着年龄的增长而持续存在.多元回归分析表明,不像睾丸激素,胰岛素样肽3对黄体生成素和性激素结合球蛋白呈负依赖性,对卵泡刺激素呈正依赖性,提示促性腺激素调节的不同机制。循环胰岛素样肽3与体重指数或腰围增加以及吸烟呈负相关,与睾丸激素不同,它不受肥胖个体体重减轻的影响。欧洲平均胰岛素样肽3的地理变化似乎在很大程度上可以通过这些参数的差异来解释。结果允许建立胰岛素样肽3的欧洲范围参考范围(95%置信区间),以适应年龄的增长。
胰岛素样肽3是Leydig细胞功能能力的组成型生物标志物,可靠可测量的肽不受促性腺激素依赖性短期调节和睾酮个体内变异的影响。
Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell-produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin-like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes.
To characterize insulin-like peptide 3 as a biomarker to assess gonadal status in aging men.
A large European multicenter (European Male Aging
Study) cohort of community-dwelling men was analyzed to determine how insulin-like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters.
Insulin-like peptide 3 declines cross-sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin-like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin-like peptide 3 is negatively dependent on luteinizing hormone and sex hormone-binding globulin and positively dependent on follicle-stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin-like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin-like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European-wide reference range for insulin-like peptide 3 (95% confidence interval) adjusted for increasing age.
Insulin-like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin-dependent short-term regulation and within-individual variation in testosterone.