TRANSFORMING GROWTH FACTOR-ALPHA IS A POTENTIAL MEDIATOR OF ESTROGEN ACTION IN THE MOUSE UTERUS

To better understand the role of peptide growth factors in sex steroid hormone-mediated growth of the female reproductive tract, the effect of estrogen on the expression of transforming growth factor-alpha (TGFalpha) in mouse uterus was investigated. Our results show that estrogen induces the expression of TGFalpha mRNA in the mouse uterus in a dose- and time-dependent manner. The up-regulation of TGFalpha transcripts occurs predominantly in uterine epithelial cells. RIA and Western blot analysis demonstrate that immunoreactive TGFalpha protein is secreted at high levels into mouse uterine luminal fluid after estrogen treatment. The induction of uterine TGFalpha mRNA is specific to estrogen; nonestrogenic steroids did not induce expression. Antibody specific to TGFalpha significantly reduces estrogen-mediated uterine growth, which supports the concept that TGFalpha is a mitogen for the reproductive tract. Analysis of TGFalpha/EGF receptors by binding, affinity labeling, and phosphorylation studies indicates that functional receptors are present in the mouse uterus after estrogen exposure. Thus, our data support a physiological role for TGFalpha and its receptor pathway in the female mouse reproductive tract.