Abstract：
Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.
摘要：
胰岛素样肽3（INSL3）是男性Leydig细胞功能能力的循环生物标志物，也表明睾丸间质细胞功能不全(LCI)和潜在的原发性性腺功能减退症。利用大型队列研究的结果，我们探索了生物学和技术差异的来源，并建立成年男性的参考范围。它是组成型分泌的，个体内部变化很小，反映了睾丸产生睾丸激素的能力。可用的主要INSL3测定法表明良好的一致性，技术差异低；没有种族影响。INSL3随年龄从35岁下降，每十年约15%。就像低计算的游离睾丸激素，以及较低程度的总睾酮水平，降低INSL3与年龄相关发病率的增加显着相关，包括较低的整体性功能，反映LCI。因此,低INSL3（≤0.4ng/ml；约在评估功能性性腺功能减退（迟发性性腺功能减退，LOH），其中睾丸激素在边界低范围内。排除低LCI（INSL3≤0.4ng/ml）的个体，导致INSL3在性腺正常人群中的年龄无关（>35岁）参考范围（血清）为0.4-2.3ng/ml，与低INSL3前瞻性识别个体有未来发病率增加的风险。
