Insulin-like factor 3 (INSL3): a new parameter to assess Leydig cell functionality and primary hypogonadismus in the EMAS population.

胰岛素样因子3 （INSL3）是睾丸间质细胞特有的组成产物。在成年男性中，它被大量分泌到血液中，从而以一种独立于睾酮并通过HPG轴反馈的方式揭示了间质细胞的功能能力。因此，它是健康和疾病中间质细胞能力的一种极好的独立测量方法，特别是在衰老过程中。我们与曼彻斯特大学的Fred Wu教授和EMAS（欧洲男性衰老研究）项目协调员合作，研究欧洲男性衰老的生理和临床病理，我们计划测量EMAS队列（总共约6000个样本）的两条腿中的INSL3。允许横断面和纵向相关性的许多生化和临床参数已经获得了最广泛的研究老年男性从八个欧洲中心。测量INSL3将不仅仅作为一个额外的参数，而且将更好地帮助确定具体的病理和临床相关的男性群体。低雄激素血症是男性衰老相关病理的核心，然而，睾酮作为临床参数受到许多混杂因素的困扰，因此性腺功能低下与年龄相关症状的因果关系难以确定。因此，对雄激素治疗的任何建议在很大程度上仅限于少数极端病例。由于INSL3是一个强大的组成参数，在很大程度上独立于这些雄激素相关的混杂因素，因此在EMAS队列中测量INSL3将为睾丸衰老在年龄相关病理（如代谢综合征或骨质疏松症）的病因学中的作用提供有价值的见解。申请人在人类（和动物）研究中测量INSL3及其临床相关性方面具有全球独特的经验。

Insulin-like factor 3 (INSL3) is a constitutive product uniquely of the testicular Leydig cells. In adult men it is secreted into the blood in substantial amounts, thereby revealing the functional capacity of the Leydig cells in a way which is independent of testosterone and feedback via the HPG axis. It is thus an excellent and independent measure of Leydig cell capacity in health and disease, especially during aging. In collaboration with Professor Fred Wu from the University of Manchester and Coordinator of the EMAS (European Male Aging Study) project to research the physiology and clinical pathology of the aging European male, we plan to measure INSL3 in the two legs of the EMAS cohort (total ca. 6000 samples), allowing both cross-sectional as well as longitudinal correlation with the many biochemical and clinical parameters already obtained in this most extensive study of aging men from eight European centres. INSL3 measurement will not simply serve as an additional parameter, but will better help to define specific pathologies and clinically relevant groups of men.Hypoandrogenemia is at the core of pathologies associated with aging in men, however, testosterone as a clinical parameter is beset with many confounders, so that a hypogonadal causality in age-related symptoms is difficult to ascertain. Consequently, any recommendation for an androgen-based therapy is largely limited to a few extreme cases only. Because INSL3 is a robust and constitutive parameter which is largely independent of these androgen-related confounders, its measurement in the EMAS cohort will provide valuable insight into the role of testicular aging in the etiology of age-related pathologies such as metabolic syndrome or osteoporosis. The applicants draw on worldwide unique experience in the measurement of INSL3 in human (and animal) studies, and its clinical relevance.