ESTROGEN INDUCES EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR AND ITS LIGANDS IN HUMAN FALLOPIAN-TUBE - INVOLVEMENT OF EGF BUT NOT TRANSFORMING GROWTH-FACTOR-ALPHA IN ESTROGEN-INDUCED TUBAL CELL-GROWTH IN-VITRO

We studied the estrogen-dependent expression of epidermal growth facto r (EGF), transforming growth factor (TGF)alpha, and EGF receptor gene transcripts in human fallopian tubes in vivo and in vitro. Competitive polymerase chain reaction (PCR) was performed on the fallopian tube R NA samples from the postmenopausal women with or without estrogen repl acement. Amounts of EGF, TGF alpha, and EGF receptors gene transcripts in the estrogen-treated group (n = 3) were significantly (P < 0.01) m ore than those in the untreated group (n = 3). Competitive PCR also sh owed that EGF, TGF alpha, and EGF receptor gene transcripts level in t ubal cells were increased by estrogen in vitro: messenger RNA levels o f these factors were significantly (P < 0.01, n = 3) increased in cell s incubated with 10(-8) M estrogen compared with those in cells withou t estrogen treatment. We studied whether EGF and/or TGF alpha is invol ved in the estrogen-induced tubal cell growth in vitro. Estrogen enhan ced the [H-3]-thymidine incorporation into the cell in dose- and time- dependent manners in culture: estrogen treatment for more than 12 h si gnificantly (P < 0.05) enhanced the [H-3]-thymidine incorporation into the cell at 10(-8) M. The estrogen-induced cell growth was observed i n association with the increase in EGF, TGF alpha, and EGF receptor me ssenger RNA levels by estrogen. If the EGF and/or TGF alpha is involve d in the cell growth, then the estrogen-induced cell growth should be suppressed by blocking the action of EGF and/or TGF alpha. Therefore, we examined the effects of neutralizing monoclonal antibodies against EGF, TGF alpha, and EGF receptors. Anti-EGF antibody significantly red uced the estrogen-induced increase in [H-3]-thymidine incorporation, w hereas anti-TGF alpha antibody failed to show the effect. Anti-EGF rec eptor antibody showed a significant suppressive effect on the estrogen -induced increase in [H-3]-thymidine incorporation. Moreover, the grow th inhibitory effect by 1 mu g/ml anti-EGF was restored by 10(-8) M EG F but not by TCF alpha even at 10(-6) M. All these data suggest that e strogen induces EGF and TGF alpha/EGF receptors in the human fallopian tube and that EGF but not TGF alpha may be involved in the estrogen-i nduced human tubal cell growth in vitro.