Regulation of high- and low-affinity epidermal growth factor receptors by glucocorticoids

It is reported that receptors for epidermal growth factor (EGF) in HeLa S3 cells exist in two forms, which differ in both affinity and capacity. Both the number of receptors and their distribution into low- and high-affinity forms are modulated by glucocorticoids. Scatchard analysis of saturation binding assays performed at 0 degrees C indicates that there is a low-affinity class of receptors (Kd approximately equal to 1.5 nM), which contains approximately 6 X 10(4) binding sites per cell, and a second, high-affinity class of receptors (Kd approximately equal to 0.16 nM) containing approximately 5 X 10(3) binding sites per cell. Exposure of HeLa S3 cells to 10(-7) M dexamethasone for 24 h increased EGF binding to whole cells by increasing the numbers of low- and high-affinity receptors by 20 and 114%, respectively. The increase in EGF binding depends upon the dose of dexamethasone, being raised from 10(-11) to 10(-6) M. EGF binding is half-maximal near 2-4 X 10(-9) M, a concentration equal to the Kd of dexamethasone for the glucocorticoid receptor in these cells. The increase in EGF binding is specific for glucocorticoids, occurring when the HeLa S3 cells are exposed to 10(-7) M cortisol or dexamethasone for 24 h, but not when the cells are similarly treated with testosterone, 5 alpha-dihydroxytestosterone, 17 beta-estradiol, or progesterone. The effect on EGF binding appears to be biphasic; the initial rapid increase occurs between 8 and 12 h, is blocked by both 10(-6) M cyclohexamide and 0.1 micrograms/ml actinomycin D, and is followed by a more gradual increase thereafter. These data indicate that glucocorticoids are able to regulate both the number of EGF receptors and their distribution into high- and low-affinity components.