Mediation by epidermal growth factor of the estradiol-induced increase in cyclic guanosine 3',5'-monophosphate content in the rat uterus.
Estrogen treatment of immature or ovariectomized mature rats induces an increase in uterine cGMP content, with a peak 2-3 h after hormone administration. This response to estrogenic action also develops in vitro, in incubated uterine horns, thus excluding the intervention of another organ. Its function is still unknown. We show here that treatment of incubated uterine horns from immature or mature rats with 8 nM epidermal growth factor (EGF), exactly mimicked the effect of 1 nM estradiol on cGMP levels. The estradiol-induced increase in uterine cGMP was canceled in the presence of the phosphotyrosine kinase inhibitor genistein. Like the cGMP response to EGF, the estradiol-induced increase in uterine cGMP was completely suppressed in the presence of an antimouse EGF antibody. On the other hand, whereas the induction of cGMP accumulation by estradiol in vivo or in vitro was suppressed by prior treatment of the animals with the pure antiestrogen ICI 164,384, such pretreatment had no effect on the EGF-induced increase in uterine cGMP content. Together, these data support the concept that the uterine cGMP response to estrogens is entirely due to auto/paracrine mediation by the EGF-EGF receptor system. Considering reports from the literature showing that EGF can directly induce the phosphorylated active form of the estrogen receptor, we speculate that this might implicate its action on cGMP, with the latter then intervening as cofactor of the involved phosphokinase(s).
Galand
P
P
Laboratoire de Cytologie et de Cancérologie Expérimentale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Rooryck
J
J
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D019833:Genistein; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D010052:Ovariectomy; D053284:Polyunsaturated Alkamides; D011374:Progesterone / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D000906:Antibodies; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D007529:Isoflavones; D053284:Polyunsaturated Alkamides; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; C051781:ICI 164384; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D006152:Cyclic GMP