School of Biosciences, University of Nottingham, University Park, Nottingham, UK.
School of Mathematics, University of Nottingham, University Park, Nottingham, UK.
Andrology. 2022 Oct;10(7):1328-1338. doi: 10.1111/andr.13220. Epub 2022 Jul 11.
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.
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/衰竭以及肿瘤发病率增加，其中一些与睾丸间质细胞产生的睾酮水平下降有关。高天然生物变异性，以及多种可以调节循环睾酮浓度的因素，可能会影响其解释和临床意义。胰岛素样肽 3 是睾丸间质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 作为评估老年男性性腺状态的生物标志物进行特征描述。
对一个大型欧洲多中心（欧洲男性衰老研究）社区居住男性队列进行了分析，以确定胰岛素样肽 3 如何与一系列激素、人体测量学和生活方式参数相关。
与睾酮不同，胰岛素样肽 3 从 40 岁起以大约每年 15%的速度进行横断面和纵向下降，而睾酮则以每年 1.9%的速度下降，部分由垂体促黄体生成素产生增加来补偿。重要的是，年轻男性的胰岛素样肽 3 水平似乎随着年龄的增长而持续下降。多元回归分析表明，与睾酮不同，胰岛素样肽 3 受黄体生成素和性激素结合球蛋白的负依赖，受卵泡刺激素的正依赖，表明其促性腺激素调节机制不同。循环胰岛素样肽 3 与体重指数或腰围增加和吸烟呈负相关，与睾酮不同，它不受肥胖个体减肥的影响。欧洲范围内平均胰岛素样肽 3 的地理差异似乎主要归因于这些参数的差异。结果允许建立一个调整年龄增长的欧洲范围内的胰岛素样肽 3（95%置信区间）参考范围。
胰岛素样肽 3 是睾丸间质细胞功能能力的固有生物标志物，是一种稳健、可靠的可测量肽，不受促性腺激素依赖性短期调节和个体内睾酮变化的影响。
