Developmental regulation of insulin-like growth factor binding protein production: studies in fetal, postnatal, and pregnant sheep

Abstract

To assess the roles of developmental factors in the regulation of sheep IGFBP production at the cellular level, we characterized and compared the IGFBPs released by fetal, postnatal, and maternal sheep skin fibroblasts in culture with those in fetal, postnatal, and maternal sheep plasma. Sheep fibroblasts produced seven IGFBPs: a 36.5-41 kDa protein induced in vitro by IGF-I, likely representing oIGFBP-3; a 28.5 kDa protein that reacted with antisera to human IGFBP-2, likely representing oIGFBP-2; 25 and 27 kDa proteins induced in fetal fibroblasts by IGF-I; a 22 kDa protein that was inhibited by IGF-I, likely representing oIGFBP-4; and 21 and 23 kDa proteins labelled only by IGF-II, suggesting their similarities to IGFBP-6. The developmental pattern of IGFBP production by sheep fibroblasts in culture was similar in several respects to that observed in sheep plasma. For example, relative amounts of the 21, 22, and 28.5 kDa IGFBPs exceeded that of the 36.5-41 kDa protein in early fetal fibroblast conditioned media and in fetal plasma, while the relative concentrations of the 36.5-41 kDa protein increased markedly during the perinatal period. Sheep plasma differed, however, in two major respects from fibroblast conditioned media: First, fetal, and to a far lesser extent maternal, plasma contained a 200 kDa IGF-II-selective BP, likely to be the circulating form of the IGF-II receptor; and second, plasma, unlike conditioned media, contained a 26 kDa IGFBP, likely to be oIGFBP-1. The results of our studies suggest that the production and release of IGFBPs by isolated sheep fibroblasts is regulated by developmental factors operative under in vitro culture conditions. The differences in the relative levels of IGFBPs in conditioned media from fetal, postnatal, and maternal sheep fibroblasts resemble in several respects the differences in the relative concentrations of the various IGFBPs in fetal, postnatal, and maternal sheep plasma. Thus, sheep fibroblasts provide a useful though imperfect model system by which to examine the nutritional and hormonal regulation of sheep IGFBP production at various developmental stages.