ABSTRACT
BACKGROUND: Insulin-like growth factors (IGFs) are anabolic proteins that are essential regulators of cell division, differentiation and growth. We describe the longitudinal changes in IGF-I, IGF-II and the binding proteins IGFBP-1, -2 and -3 before and during normal pregnancy. METHOD: Serum samples were taken before conception and then at 12, 24 and 36 weeks of gestation in 41 healthy women with uncomplicated pregnancies. We measured IGF-I using an automated chemiluminescent method, IGF-II and IGFBP-2 using in-house radioimmunoassays (RIAs), and IGFBP-1 and IGFBP-3 using commercial enzyme-linked immunosorbent assay (ELISA) and RIA kits, respectively. Because of the potential haemodilution effects during pregnancy, albumin was also measured in all samples. RESULTS: There was a significant fall in IGF-I during the first (36%) and second trimesters (21%) followed by an increase of 25% at 36 weeks. During pregnancy, the mean IGF-II concentrations fell by 12% at 12 weeks, 8% at 24 and 8% at 36 weeks compared with pre-conception values. When IGF-II results were adjusted for the haemodilution of pregnancy, its concentrations increased. During pregnancy, there was a rapid increase in mean IGFBP-1 levels by 17-fold (12 weeks), 24-fold (24 weeks) and 25-fold (36 weeks). IGFBP-2 concentrations fell after conception but started to increase towards term. This increase was more significant when adjusted for haemodilution. In contrast, IGFBP-3 concentrations increased significantly throughout pregnancy. CONCLUSION: Our data on the physiological changes of IGFs and their binding proteins add further evidence of the vital roles of these hormones throughout normal pregnancy.
Subject(s)
Longitudinal Studies , Pregnancy/blood , Somatomedins/analysis , Biomarkers/blood , Birth Weight , Enzyme-Linked Immunosorbent Assay , Female , Gestational Age , Hemodilution , Humans , Infant, Newborn , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Luminescent Measurements , Male , Radioimmunoassay , Somatomedins/metabolism , Statistics as TopicABSTRACT
BACKGROUND: Maternal calcium homeostasis adapts during pregnancy to provide for the needs of the growing fetal skeleton. Wide selections of bone turnover markers are currently available to assess the changes taking place; here, data are presented on two serum-based markers. METHODS: The use of serum-based biochemical bone turnover markers during pregnancy was assessed in a cohort of 41 women recruited prior to conception. Serum N-terminal extension peptide of procollagen (P1NP) was used to monitor bone formation and serum beta-crosslaps (S-CTX) used to assess resorption. Blood samples were measured at five time points from a pre-conceptual baseline, through pregnancy, to the final sample, which was taken within 1 week of delivery. RESULTS: An initial decrease from the baseline in both P1NP and S-CTX was observed at 12 weeks; however, it is suggested that this may be due to the haemodilutional effect of pregnancy rather than a true change in bone turnover. Significant increases from the baseline of both analytes were observed by 36 weeks (P1NP, P = 0.013; S-CTX, P = 0.002), when the calcium demands of the fetus are greatest. CONCLUSIONS: This study illustrates the use of serum-based bone turnover markers to assess turnover during normal pregnancy, a time when ionizing radiation cannot be used to assess bone turnover.
Subject(s)
Bone Remodeling/physiology , Pregnancy/blood , Adult , Biomarkers/blood , Calcium/blood , Female , Humans , Procollagen/blood , Time FactorsABSTRACT
The effects of the 1-34 N-terminal parathyroid hormone-related protein fragment (0-10 microM) and the 67-86 parathyroid hormone-related protein fragment (0-10 microM) on trophoblast apoptosis, induced by TNFalpha and IFN-gamma or by the protein kinase inhibitor staurosporine, were investigated. TNFalpha/IFN-gamma and staurosporine significantly increased the rate of apoptosis by fivefold and by eightfold, respectively. Parathyroid hormone-related protein (1-34) evoked a dose-dependent rescue of both TNFalpha/IFNgamma-induced and staurosporine-induced apoptosis, whereas parathyroid hormone-related protein (67-86) had no significant effect on staurosporine-induced apoptosis, and only significantly diminished TNFalpha/IFNgamma-induced apoptosis at 10 microM. Parathyroid hormone-related protein was thus found to be a cytotrophoblast apoptosis survival factor.
