Rat pituitary GC cell insulin-like growth factor-I receptor regulation

Exposure of rat GC pituitary cells to insulin-like growth factor-I (IGF-I) resulted in a time- and concentration-dependent reduction in cell surface IGF-I receptor binding. Preincubation of cells with 6.5 nM IGF-I for 24 h caused an approximately 50% reduction of the number of cell surface receptors. Scatchard analysis revealed that the number of IGF-I cell surface receptors decreased from 18,500 to 9,100 sites/cell, with no apparent alteration in the affinity of IGF-I receptor for its ligand. The level of IGF-I receptor mRNA, however, was not altered by preincubating cells for up to 24 h with 6.5 nM IGF-I. The sequestered IGF-I receptors reappeared on the cell membrane and return to their preincubation surface distribution within 3 h after removal of IGF-I. These results support the notion that down-regulation of somatotroph IGF-I receptors involves translocation of cell surface receptors to the intracellular pool, and this effect is reversed by removal of IGF-I ligand.