Free IGF-I, IGFBP-1, and the Binary Complex of IGFBP-1 and IGF-I Are Increased during Human Pregnancy

Abstract

Background/Aims: To investigate changes in free insulin-like growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP-1) complexed IGF-I during human pregnancy. Methods: Overnight fasting serum was obtained in a longitudinal design from 11 women with non-complicated pregnancy at gestation weeks 6–10, 16–20, 24–28 and 35–38 and, for comparison, 5 weeks post-partum. All samples were analyzed for total and free IGF-I and IGF-II, IGFBP-3 and IGFBP-3 proteolysis, total and non-phosphorylated (np-) IGFBP-1, and IGFBP-1 complexed IGF-I. Results: Total IGF-I was increased in late pregnancy (week 35–38) (p < 0.001), whereas free IGF-I was significantly increased by 77% already at week 6–10 (p = 0.004) and by 140% (p = 0.002) at week 34–38, when compared to post-partum levels. At weeks 16–20 and 24–28, levels of free IGF-I were not significantly different from post-partum levels. Significant IGFBP-3 proteolysis was detectable from week 6–10 and throughout pregnancy (p < 0.05). Total and np-IGFBP-1 were significantly increased from 16–20 weeks of pregnancy (both p < 0.05) and IGFBP-1 complexed IGF-I was increased 2-fold from week 16–20 and throughout pregnancy (p < 0.05). However, the saturation of IGFBP-1 remained constant at 27–29% during the study. Conclusion: We found evidence of increased free IGF-I and increased IGF-I in binary complexes during pregnancy, possibly caused by IGFBP-3 proteolysis and decreased ternary complex formation.

The Impacts of Fish Oil and/or Probiotic Intervention on Low-Grade Inflammation, IGFBP-1 and MMP-8 in Pregnancy: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial

“…We showed that serum hsCRP and MMP-8 decreased while IGFBP-1 and phIGFBP-1 increased during pregnancy, regardless of the intervention or GDM status. Our findings with respect to the changes of IGFBP-1 and hsCRP during pregnancy are in agreement with the results of previous studies [60][61][62][63] but some discrepancies exist regarding hsCRP, e.g., a study conducted in non-obese pregnant women with GDM detected an elevation in hsCRP along with the gestational age [64]. The MMP-8 level declined, which is in contrast to previous studies in which increased MMP-8 levels were related to adverse pregnancy outcomes including preterm delivery [65] or high amniotic fluid MMP-8 in intra-amniotic inflammation [5].…”

Longitudinal Study of the Maternal Insulin-Like Growth Factor System before, during and after Pregnancy in Relation to Fetal and Infant Weight

“…However, as discussed previously [21], their nutritional status is probably typical of that of Swedish women and not very different from women in other developed countries. Regarding the variability of the maternal IGF system components before, during and after pregnancy, our observations were similar to those reported for other study populations [4, 10, 13]. The changes we observed during pregnancy are also in agreement with results obtained in other Western populations for IGF-I [4, 10, 13], IGF-II [4, 10, 13], IGFBP-1 [4, 10], IGFBP-3 [10, 11, 13] and protease activity against IGFBP-3 [13,14,15].…”

“…However, high concentrations of IGFBP-1 in maternal serum will decrease circulating ‘free’ IGF-I inhibiting this anabolic effect, thus counteracting fetal growth. Such a mechanism can be reconciled with observations showing that serum concentrations of ‘free’ IGF-I are markedly increased during late pregnancy [13]. …”

“…Thus, serum concentrations of IGF-I decrease during the first trimester [4, 10] and increase gradually throughout the remaining two trimesters [4,10,11,12,13], whereas concentrations of IGF-II remain relatively unchanged throughout gestation [10, 13]. The serum concentrations of IGFBP-3 increase gradually during pregnancy [4, 10], while those of IGFBP-1 are increased in the first trimester and remain high until delivery [4, 10, 12, 13]. In addition, during pregnancy, IGFBP-3 is degraded by proteases to a considerable extent [13,14,15], possibly produced by the decidua [14].…”

“…The serum concentrations of IGFBP-3 increase gradually during pregnancy [4, 10], while those of IGFBP-1 are increased in the first trimester and remain high until delivery [4, 10, 12, 13]. In addition, during pregnancy, IGFBP-3 is degraded by proteases to a considerable extent [13,14,15], possibly produced by the decidua [14]. It is conceivable that this results in a decreased affinity of IGFBP-3 for IGF-I and consequently in increased amounts of ‘free’ IGFs available for receptors in various maternal tissues as well as in the placenta [16].…”