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

Abstract

It is reported that receptors for epidermal growth factor (EGF) in HeLa S 3 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 °C indicates that there is a low-affinity class of receptors ( K d ≊ 1.5 nm ), which contains approximately 6 × 10 4 binding sites per cell, and a second, high-affinity class of receptors ( K d ≊ 0.16 nm ) containing approximately 5 × 10 3 binding sites per cell. Exposure of HeLa S 3 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 × 10 −9 m, a concentration equal to the K d of dexamethasone for the glucocorticoid receptor in these cells. The increase in EGF binding is specific for glucocorticoids, occurring when the HeLa S 3 cells are exposed to 10 −7 m cortisol or dexamethasone for 24 h, but not when the cells are similarly treated with testosterone, 5α-dihydroxytestosterone, 17β-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 μg/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. Press, Inc.