Characterization of insulin-like growth factor i receptors in the median eminence of the brain and their modulation by food restriction

High affinity binding sites for ¹²⁵I-labeled [Thr⁵⁹]insulin-like growth factor I (IGF-I) were measured in rat median eminence by in vitro autoradiography with slidemounted sections of frozen rat brain. Specific binding of 0.1 nM iodo-[Thr⁵⁹]IGF-I to brain slices reached maximum by 12 h at 4 C and was unchanged at 24 h. Densitometry by computer digital image analysis of autoradiographic images indicated that specific binding of iodo-[Thr⁵⁹]IGF-I to the median eminence was reversible. The specificity of binding was evaluated with competition of iodo-[Thr⁵⁹]IGF-I with unlabeled [Thr⁵⁹]IGF-I, ratlGFII (multiplication-stimulating activity), and porcine insulin. All were recognized by the binding site, but the rank order of potency was [Thr⁵⁹]IGF-I < IGF-II < insulin. Somatostatin was completely ineffective. Further, an antibody against the rat IGF-II receptor did not block binding of iodo-[Thr⁵⁹]IGF-I to the median eminence. Fourteen days of food restriction (75% of food intake of controls) resulted in significant weight loss and reduction of plasma immunoreactive IGF-I in six food-restricted rats (0.9 ±0.1 U/ml) compared with values in six controls (2.6 ± 0.5 U/ml; P < 0.001). Binding of 125I-labeled [Thr⁵⁹]IGF-I in the median eminence was significantly increased in the food-restricted rats, primarily due to an increase in the concentration of iodo-[ThrS9]IGF-I-binding sites in the median eminence; the affinity (Kd) of binding was unchanged. The results indicate that the median eminence has type I IGF-I receptors, which become more numerous under metabolic conditions associated with decreased caloric intake and lowered plasma IGF-I levels.