Co-administration of IGF-binding protein-3 differentially inhibits the IGF-I-induced total body and organ growth of Snell dwarf mice

In mammals IGF-I is part of a 150-kDa binding protein complex, which also contains a glycosylated acid-labile protein (ALS) and a glycosylated acid-stable IGF binding subunit IGFBP-3. Administration of free IGF-I in vivo induces not only acute insulin-like effects but also growth stimulation. Since co-injection with IGFBP-3 only partially blocked the hypoglycemic response of free IGF-I in hypophysectomized rats, we were interested in the growth stimulating activity of the IGFI-IGFBP-3 complex in pituitary-deficient mice compared to that obtained by IGF-I alone. Therefore, the effects of subcutaneously administered IGF-I, IGFBP-3 and the IGF-I-IGFBP-3 complex on somatic growth and organ growth of pituitary-deficient Snell dwarf mice were studied after 4 weeks of treatment.

Treatment with IGF-I alone induced a significant increase in body length and weight, as well as in weights of the submandibular salivary glands, kidneys and quadriceps femooris muscles as compared to buffer treated controls. No significant changes were found in liver, brain, heart and thymus. IGFBP-3 alond had no effect. However, the stimulating effects of IGF-I alone on body length and weight, as well as on the weight of the kidneys, were fully neutralized by co-injection with IGFBP-3. In contrast, the weights of submandibular salivary glands and m. quadriceps femoris were increased by treatment with the complex compared to controls and not significantly different from animals treated with IGF-I alone.

Our data show that in GH-deficient mice administration of IGFBP-3 differentially inhibits the IGF-I induced body and organ growth. This calls for extra vigilance when exploring presumed adbantages of administering an IGF-I-IGFBP-3 complex to GH-deficient individuals in order to obtain stimulation of growth.