Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Front Endocrinol (Lausanne). 2024 Jul 1;15:1404320. doi: 10.3389/fendo.2024.1404320. eCollection 2024.
The peptide hormone Insulin-like Factor 3 (INSL3) is a biomarker of testicular Leydig cells in the male but is also expressed by the theca cells of the ovaries. With the advent of sensitive assays INSL3 can be quantified in female circulation, and we suggest that circulating INSL3 is a novel biomarker for pubertal development in girls. The aim of the study is to quantify INSL3 by LC-MS/MS in sera from normal girls during pubertal transition, and during gonadal suppression by GnRH agonist therapy in girls with central precocious puberty (CPP).
The sensitivity of an established LC-MS/MS-based method for serum INSL3 was improved by switching to a state-of-the-art triple quadruple mass spectrometer (Altis Plus, Thermo).
The limit of detection of the improved LC-MS/MS method for serum INSL3 was 0.01 ug/L (1.5 pM) and the inter-assay CV was < 12%. Serum INSL3 increased during the pubertal transition in healthy girls and changes correlated with the concomitant rise in other measured hormones. In some girls, but not all, INSL3, FSH, inhibin B and estradiol serum concentrations increased prior to first clinical signs of puberty. Serum INSL3 concentrations were increased at baseline in girls with CPP compared to prepubertal controls and decreased during treatment with GnRH agonist followed by a steep rise and normalization after cessation of treatment.
The improved method allowed for quantification of INSL3 in longitudinally collected serum samples during pubertal transition in healthy girls as well as in girls with CPP before, during and after treatment with GnRH agonist. Future studies are needed to clarify if INSL3 in combination with other biomarkers enhances the predictive value of differentiating between premature thelarche and CPP.
肽激素胰岛素样因子 3（INSL3）是男性睾丸间质细胞的生物标志物，但也在卵巢的卵泡膜细胞中表达。随着灵敏检测方法的出现，INSL3 可以在女性循环中定量，我们认为循环 INSL3 是女孩青春期发育的一种新的生物标志物。本研究的目的是通过液相色谱-串联质谱（LC-MS/MS）定量分析青春期过渡期间正常女孩和促性腺激素释放激素激动剂治疗下中枢性性早熟（CPP）女孩的血清 INSL3。
通过切换到最先进的三重四极杆质谱仪（Altis Plus，Thermo），改进了用于血清 INSL3 的 LC-MS/MS 方法的灵敏度。
改进的 LC-MS/MS 方法检测血清 INSL3 的检测限为 0.01 ug/L（1.5 pM），批内 CV 小于 12%。健康女孩青春期过渡期间血清 INSL3 增加，其变化与其他同时测量的激素升高相关。在一些女孩中（但不是所有女孩），INSL3、FSH、抑制素 B 和雌二醇血清浓度在青春期的第一临床体征出现之前增加。与青春期前对照组相比，CPP 女孩的基础血清 INSL3 浓度升高，在 GnRH 激动剂治疗期间下降，随后治疗停止后急剧上升并恢复正常。
改进的方法允许在健康女孩青春期过渡期间以及 GnRH 激动剂治疗前、治疗中和治疗后定量分析 CPP 女孩的血清 INSL3。需要进一步研究以明确 INSL3 与其他生物标志物结合是否能提高区分性早熟和 CPP 的预测价值。
