INTERDEPENDENCE OF EPIDERMAL GROWTH-FACTOR AND INSULIN-LIKE GROWTH-FACTOR-I EXPRESSION IN THE MOUSE UTERUS

Both epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been implicated as paracrine mediators of estrogen action in the rodent uterus. Here we have used a semiquantitative reverse transcription-polymerase chain reaction assay to demonstrate the changes in IGF-I messenger RNA (mRNA) and EGF mRNA abundance in response to the unilateral intraluminal administration of 17 beta-estradiol (E(2)), EGF, and IGF-I. Local administration of EGF to ovariectomized mice significantly increased IGF-I mRNA abundance compared to that in the contralateral saline-injected uterine horn (141.06 +/- 19.04% of control value; mean +/- SEM; n = 7; P = 0.031), comparable to the effect of E(2) administration (143.21 +/- 12.47% of control value; n = 7; P = 0.045). Similar results were obtained in immature mice. Pretreatment with the antiestrogen ICI 164 384 completely blocked the E(2)-induced increase and partially blocked the EGF-induced increase in IGF-I mRNA. Furthermore, intraluminal administration of sheep antibodies to EGF receptor significantly decreased the amount of IGF-I mRNA compared to that in the contralateral sheep immunoglobulin G-treated uterine horn (78.49 +/- 4.33% vs. 100 +/- 2.65%; mean +/- SEM; P = 0.014). Intraluminal administration of IGF-I significantly increased the amount of EGF mRNA in the treated uterine horn (173.33 +/- 18.79% of the control value), whereas it had no effect on IGF-I mRNA abundance. Similarly, intraluminal administration of EGF had no significant effect on uterine EGF mRNA levels. These data provide some insight into the complex interaction of growth factors that occurs in the uterus after E(2) administration and suggests that activation of IGF-I expression may be a common down-stream event in both E(2)- and EGF-induced uterine cellular proliferation. Paracrine actions of EGF, which is expressed predominantly in the epithelial cells, on IGF-I expression by stromal cells and paracrine effects of stromal IGF-I on EGF expression in epithelial cells may facilitate the epithelial-stromal interactions, which are thought to be important in E(2)-induced endometrial proliferation.