Hospital Infantil Universitario Niño Jesús, Departments of Pediatrics & Pediatric Endocrinology, Research Institute "La Princesa," Department of Pediatrics, Universidad Autónoma de Madrid, E-28009, Madrid, Spain.
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutriciόn (CIBEROBN), Instituto de Salud Carlos III, E-28009, Madrid, Spain.
J Clin Endocrinol Metab. 2022 Sep 28;107(10):2912-2924. doi: 10.1210/clinem/dgac453.
Pappalysins (PAPP-A, PAPP-A2) modulate body growth by increasing insulin-like growth factor I (IGF-I) bioavailability through cleavage of insulin-like growth factor binding proteins (IGFBPs) and are inhibited by stanniocalcins (STC1, STC2). Normative data on these novel factors, as well as on free IGF-I and uncleaved fractions of IGFBPs, are not well established.
This work aimed to determine serum concentrations of PAPP-A, PAPP-A2, STC1, and STC2 in relationship with other growth hormone (GH)-IGF axis parameters during development.
Full-term newborns (150; gestational age: 39.30 ± 1.10 weeks), 40 preterm newborns (30.87 ± 3.35 weeks), and 1071 healthy individuals (aged 1-30 years) were included in the study and divided according to their Tanner stages (males and females): I:163 males, 154 females; II:100 males, 75 females; III:83 males, 96 females; IV: 77 males, 86 females; and V:109 males,128 females.
Serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were elevated at birth and declined throughout childhood. In postnatal life, PAPP-A2 concentrations decreased progressively in concomitance with the free/total IGF-I ratio; however, stanniocalcin concentrations remained stable. PAPP-A2 concentrations positively correlated with the free/total IGF-I ratio (r = +0.28; P < .001) and negatively with the intact/total IGFBP-3 ratio (r = -0.23; P < .001). PAPP-A concentrations inversely correlated with intact/total IGFBP-4 ratio (r = -0.21; P < .001), with PAPP-A concentrations being lower in females at all ages. Association studies indicate the importance of stanniocalcins and pappalysins in the control of this axis in an age-specific manner.
This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of cleaved and uncleaved IGFBPs.
Pappalysins（PAPP-A、PAPP-A2）通过切割胰岛素样生长因子结合蛋白（IGFBPs）来增加胰岛素样生长因子 I（IGF-I）的生物利用度，从而调节身体生长，并受到 Stanniocalcins（STC1、STC2）的抑制。这些新型因子以及游离 IGF-I 和未切割的 IGFBP 片段的正常参考值尚未得到很好的建立。
本研究旨在确定 PAPP-A、PAPP-A2、STC1 和 STC2 的血清浓度与生长激素（GH）-IGF 轴参数在发育过程中的关系。
本研究纳入了 150 名足月新生儿（胎龄：39.30±1.10 周）、40 名早产儿（胎龄：30.87±3.35 周）和 1071 名健康个体（年龄 1-30 岁），并根据他们的 Tanner 阶段（男性和女性）进行了分组：I 期：163 名男性，154 名女性；II 期：100 名男性，75 名女性；III 期：83 名男性，96 名女性；IV 期：77 名男性，86 名女性；V 期：109 名男性，128 名女性。
出生时 PAPP-A、PAPP-A2、STC1、STC2、IGFBP-2、总 IGFBP-4 和总 IGFBP-5 的血清浓度升高，并在儿童期逐渐下降。在新生儿期后，PAPP-A2 浓度随着游离/总 IGF-I 比值的增加而逐渐下降；然而，Stanniocalcin 浓度保持稳定。PAPP-A2 浓度与游离/总 IGF-I 比值呈正相关（r=+0.28；P<0.001），与完整/总 IGFBP-3 比值呈负相关（r=-0.23；P<0.001）。PAPP-A 浓度与完整/总 IGFBP-4 比值呈负相关（r=-0.21；P<0.001），且所有年龄段的女性 PAPP-A 浓度均较低。关联研究表明，Stanniocalcins 和 Pappalysins 以年龄特异性的方式在控制该轴方面具有重要意义。
本研究提供了 Pappalysins 和 Stanniocalcins 的参考值，它们通过改变切割和未切割 IGFBP 的浓度来调节 IGF-I 的活性。
