The insulin-like growth factors (IGF) are important anabolic hormones in the mammalian fetus; their anabolic actions are potentially modulated by alterations in the IGF-binding proteins (IGFBP). We have previously shown that the nutritional state of the fetus affects both IGF-I and the IGFBP concentrations. The present study was designed to determine the effect of alterations in insulin and IGF-I circulating concentrations on the IGFBPs. Because both insulin and IGF-I elicit decreases in glucose and amino acid concentrations, the concentrations of these substrates were clamped during the hormone infusions. Sixteen ovine fetuses were chronically catheterized at approximately 115 days of gestation, and experimental procedures performed at approximately 130 days of gestation. Insulin, IGF-I or both were infused for an 8-h period. Baseline concentrations of hormones and binding proteins were obtained, and concentrations were also obtained at the end of the infusion. Hepatic IGFBP-1 mRNA expression was also determined. Intravenous infusion of IGF-I significantly increased IGF-I concentrations in plasma in the ovine fetus. Intravenous infusion of insulin inhibited hepatic IGFBP-1 gene expression when amino acids and glucose were clamped. In contrast, intravenous infusion of recombinant human IGF-I (rhIGF-I) enhanced hepatic IGFBP-1 gene expression. Neither insulin nor rhIGF-I treatment had an effect on hepatic IGFBP-3 gene expression. Insulin did not alter plasma IGFBP-1 significantly, but it increased IGFBP-3 in plasma. rhIGF-I increased both IGFBP-1 and IGFBP-3 protein levels in plasma. The responses of IGFBP-1 and IGFBP-3 to increased plasma IGF-I and insulin may serve to protect the fetus from exaggerated anabolic effects and to blunt the hypoglycemic potential of circulating IGFs and insulin.

This article has been cited by other articles:

				S Shaikh, F H Bloomfield, M K Bauer, H H Phua, R S Gilmour, and J E Harding Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues J. Endocrinol., July 1, 2005; 186(1): 145 - 155. [Abstract] [Full Text] [PDF]

				W. Shen, P. Wisniowski, S. C. Denne, D. W. Boyle, and E. A. Liechty Anabolic effects of insulin and IGF-I in the ovine fetus are reduced by prolonged maternal fasting Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E907 - E913. [Abstract] [Full Text] [PDF]

				M. Manikkam, E. J. Crespi, D. D. Doop, C. Herkimer, J. S. Lee, S. Yu, M. B. Brown, D. L. Foster, and V. Padmanabhan Fetal Programming: Prenatal Testosterone Excess Leads to Fetal Growth Retardation and Postnatal Catch-Up Growth in Sheep Endocrinology, February 1, 2004; 145(2): 790 - 798. [Abstract] [Full Text] [PDF]

				P. M. J. O'Connor, J. A. Bush, A. Suryawan, H. V. Nguyen, and T. A. Davis Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E110 - E119. [Abstract] [Full Text] [PDF]

				T. A. Davis, M. L. Fiorotto, D. G. Burrin, R. C. Vann, P. J. Reeds, H. V. Nguyen, P. R. Beckett, and J. A. Bush Acute IGF-I infusion stimulates protein synthesis in skeletal muscle and other tissues of neonatal pigs Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E638 - E647. [Abstract] [Full Text] [PDF]

				W. Shen, D. Mallon, D. W. Boyle, and E. A. Liechty IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E593 - E603. [Abstract] [Full Text] [PDF]