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Molecular, Cellular and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, Maryland 20892
Departments of Medicine and Medical Research Service, University of Illinois College of Medicine and Veterans Administration West Side Medical Center Chicago, Illinois 60612
Address requests for reprints to: Dr. Guck T. Ooi, Molecular, Cellular, and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Building 10, Room 8D14, Bethesda, Maryland 20892.
Abstract
The insulin-like growth factor-binding proteins IGFBP-1 and IGFBP-2 are low mol wt IGFBPs that are similar in structure. They are not glycosylated and have a homologous amino acid sequence, including the number and position of 18 cysteine residues and a carboxyl-terminal Arg-Gly-Asp sequence that can be recognized by cell adhesion receptors. The present study demonstrates that expression of mRNAs encoding the two BPs differs in some fetal rat tissues and in the livers of adult rats after hypophysectomy, fasting, or streptozotocin-induced diabetes. As determined by Northern blot hybridization using cDNA probes for rat IGFBP-2 or human IGFBP-1, both mRNAs are expressed at high levels in liver of 21-day gestation and 1-dayold rats and at lower levels in 21- and 65-day-old rat liver. Levels of both mRNAs are higher in liver than in other fetal rat tissues. The relative abundance of the two mRNAs in most fetal tissues is similar to that in liver, except that kidney and brain have 8-fold and more than 25-fold higher relative levels of IGFBP-2 mRNA, respectively. IGFBP-2 mRNA is about 10- to 20-fold increased after hypophysectomy or fasting, whereas IGFBP-1 mRNA is relatively unchanged. IGFBP-2 mRNA levels are decreased completely by refeeding fasted rats for 3 days, but only partially decreased by treatment of hypophysectomized rats with GH, cortisone acetate, T4, and testosterone for 4 days. Severe diabetes induced in rats by treatment with streptozotocin (140 mg/kg) increased IGFBP-1 mRNA 100 to 200-fold and IGFBP-2 mRNA 6- to 8-fold. Insulin treatment decreased IGFBP-1 mRNA, but not IGFBP-2 mRNA. Induction of the two IGFBP mRNAs appears to occur at different levels of insulin deficiency; IGFBP-2 mRNA is increased by mild insulinopenia in hypophysectomy and fasting, whereas IGFBP-1 mRNA is only increased in the more severe insulinopenia of diabetes. Corresponding changes have been observed in the levels of immunoreactive IGFBP-1 and IGFBP-2 in rat serum, suggesting that regulation occurs at the level of mRNA abundance. These differences in tissue-specific expression and metabolic regulation suggest that IGFBP-1 and IGFBP-2 may have unique biological functions in the fetal rat and during catabolic states in adult rats.
FOOTNOTES
* Supported in part by a Feasibility Grant from the American Diabetes Association and a Research Career Development Award from the V.A.
Received for publication October 5, 1989. Revision received November 14, 1989. Accepted for publication November 21, 1989.
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