Regulation of epidermal growth factor receptor by estrogen.
Administration of 17 beta-estradiol (E2) to immature female rats produces a 3-fold increase in 125I-epidermal growth factor (EGF) binding to uterine membranes with no change in the affinity of membrane receptors for EGF. E2 treatment also increases the EGF receptor visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after affinity labeling of uterine membranes and the EGF-stimulated receptor autophosphorylation activity. In addition, E2 administration stimulates EGF-dependent tyrosine kinase activity in an assay system using exogenous angiotensin II as substrate. Following hormone treatment, EGF receptor levels increase between 6 and 12 h, remain elevated at 18 h, and decline between 24 and 36 h. This stimulation of EGF receptor levels by E2 is specific, since the non-estrogenic hormones progesterone, dexamethasone, and dihydrotestosterone fail to elevate receptor levels. E2-stimulated increases in EGF receptor levels are also blocked by cycloheximide and actinomycin D, suggesting that the observed effect represents de novo synthesis of the EGF receptor and may be mediated by a transcriptional mechanism. These results demonstrate that estrogen can regulate acutely the levels of EGF receptor in vivo and raise the possibility that events coupled to this receptor may play a role in estrogen-stimulated growth.
Mukku
V R
VR
Stancel
G M
GM
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
D004967:Estrogens; D011956:Receptors, Cell Surface; D013196:Dihydrotestosterone; D003609:Dactinomycin; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D003513:Cycloheximide; D066246:ErbB Receptors