Binding proteins for the insulin-like growth factors (IGFBPs) modulate the actions of IGF I and IGF II. IGFBP-2 is particularly high in plasma of pregnant and fetal animals and in milk. We investigated the peri-lactational control of IGFBP-2 expression and secretion. Fifteen singleton-bearing pregnant ewes at day 101 of gestation were injected sc twice daily for 8 days with bovine growth hormone (bGH) or ovine placental lactogen (oPL) both at 0.15 mg·kg−1·d−1 or saline. A further fifteen ewes at day 17 of lactation were injected sc twice daily for 5 days with bGH or oPL at 0.1 mg·kg−1·d−1 or saline. On the last day of injection blood samples were taken and the animals were sacrificed. Liver and mammary tissue samples were immediately frozen and subsequently extracted to provide total RNA for evaluation by Northern blot analysis using a rat IGFBP-2 cDNA probe. Plasma samples were analysed by Western ligand blotting for IGFBP-2. The comparison of the two saline-treated groups (pregnant vs lactating ewe) revealed no difference in the plasma concentrations of IGFBP-2. IGFBP-2 mRNA expression in the liver of the lactating ewes was markedly increased compared to that in the pregnant ewes. In contrast, in mammary tissue the expression was significantly lower in lactating than in pregnant sheep. In pregnant animals treatment with bGH, but not oPL, decreased the expression of IGFBP-2 in liver. There was a similar trend in the lactating ewe. GH treatment, but not PL treatment, moderately reduced IGFBP-2 levels in the lactating but not the pregnant ewes. bGH but not oPL induced hyperinsulinaemia. We conclude that GH has actions in pregnancy and lactation which are not mimicked by oPL. The regulation of hepatic IGFBP-2 expression by GH is similar in pregnant and postpartum animals. However, there are distinct differences in the tissue-specific regulation of IGFBP-2 between pregnancy and lactation. The liver might be the major source of circulating IGFBP-2.
M Klempt, BH Breier, SH Min, DDS MacKenzie, SN McCutcheon and PD Gluckman
BW Gallaher, MH Oliver, K Eichhorn, U Kessler, W Kiess, JE Harding, PD Gluckman and BH Breier
Gallaher BW, Oliver MH, Eichhorn K, Kessler U, Kiess W, Harding JE, Gluckman PD, Breier BH. Circulating insulin-like growth factor II/mannose-6-phosphate receptor and insulin-like growth factor binding proteins in fetal sheep plasma are regulated by glucose and insulin. Eur J Endocrinol 1994; 131:398–404. ISSN 0804–4643
We have reported previously that levels of insulin-like growth factor I (IGF-I) and IGF-II in fetal sheep plasma decrease with maternal starvation and increase following an infusion of glucose to the starved fetus, while a fetal infusion of insulin elevates UGF-I alone. We now report the changes in the circulating IGF-II/M6P receptor and plasma IGF binding proteins (IGFBPs), as measured by western blotting and ligand blotting, respectively, in fetus and mother during this study. In fetal plasma, the circulating IGF-II/mannose-6-phosphate (M6P) receptor, IGFBP-3 and IGFBP-4 were reduced during starvation. While circulating IGF-II/M6P receptor and IGFBP-4 levels were increased following the fetal insulin or glucose infusion, IGFBP-3 was unchanged and increased only after 48 h of maternal refeeding. Both IGFBP-1 and IGFBP-2 increased with starvation but while IGFBP-1 levels returned to control values following both insulin and glucose infusion, levels of IGFBP-2 were not reduced significantly by either infusion or by refeeding. In maternal plasma, levels of IGFBP-3 and IGFBP-4 decreased while IGFBP-1 and IGFBP-2 increased after 48 h of starvation. Levels of each IGFBP were unaltered following the fetal infusions but returned to values obtained during the control period after refeeding. These data show that each of the IGF carrier proteins is sensitive of changes in nutrition, either acutely, such as IGFBP-1, or chronically, as for IGFBP-3. This suggests that the circulating IGFII/M6P receptor and the IGFBP's may modulate IGF activity in the fetus during different nutritional states.
BH Breier, Research Centre for Developmental Medicine and Biology, Department of Paediatrics, School of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand