DIFFERENT TISSUE DISTRIBUTION AND HORMONAL-REGULATION OF MESSENGER-RNAS ENCODING RAT INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 AND PROTEIN-2

The insulin-like growth factor-binding proteins IGFBP-1 and IGFBP-2 are low mol wt IGFBPs thatare similar in structure. They are not glycosylatedand 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 adhesionreceptors. The present study demonstrates thatexpression of mRNAs encoding the two BPs differsin some fetal rat tissues and in the livers of adultrats after hypophysectomy, fasting, or streptozoto-cin-induced diabetes. As determined by Northernblot hybridization using cDNA probes for rat IGFBP-2 or human IGFBP-1, both mRNAs are expressed athigh levels in liver of 21-day gestation and 1-day-old rats and at lower levels in 21- and 65-day-old ratliver. Levels of both mRNAs are higher in liver thanin other fetal rat tissues. The relative abundance ofthe two mRNAs in most fetal tissues is similar tothat in liver, except that kidney and brain have 8fold and more than 25-fold higher relative levels ofIGFBP-2 mRNA, respectively. IGFBP-2 mRNA isabout 10- to 20-fold increased after hypophysectomy or fasting, whereas IGFBP-1 mRNA is relativelyunchanged. IGFBP-2 mRNA levels are decreasedcompletely by refeeding fasted rats for 3 days, butonly partially decreased by treatment of hypophy-sectomized rats with GH, cortisone acetate, T4, andtestosterone for 4 days. Severe diabetes induced inrats 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 occurat different levels of insulin deficiency; IGFBP-2mRNA is increased by mild insulinopenia in hypophysectomy and fasting, whereas IGFBP-1 mRNA isonly increased in the more severe insulinopenia ofdiabetes. Corresponding changes have been observed in the levels of immunoreactive IGFBP-1 andIGFBP-2 in rat serum, suggesting that regulationoccurs at the level of mRNA abundance. These differences in tissue-specific expression and metabolic regulation suggest that IGFBP-1 and IGFBP-2may have unique biological functions in the fetal ratand during catabolic states in adult rats. © 1990 by The Endocrine Society.