Uterine Insulin-Like Growth Factor-I Receptors: Regulation by Estrogen and Variation throughout the Estrous Cycle*

Abstract

This study was undertaken to identify uterine insulin-like growth factor-I (IGF-I) receptors and examine the regulation of these receptors throughout the estrous cycle and after 17 beta-estradiol (E2) administration to immature rats. We have demonstrated type I IGF receptors in crude uterine membranes by binding and cross-linking experiments. The characteristics of the uterine IGF-I receptor are similar to those reported for other tissues, with a high affinity component (Kd = 0.12 nM; binding capacity = 0.028 pmol/mg protein) and a low affinity component (Kd = 0.98 nM; binding capacity = 0.041 pmol/mg protein). Autoradiographic visualization of [125I]IGF-I binding to uterine sections localized the IGF-I receptors to the smooth muscle cells of the myometrial layer of the uterus, with a higher density of IGF-I receptors in the outer longitudinal layer than in the inner circular layer. In immature rats administration of E2 significantly increased total [125I]IGF-I binding per uterus as early as 6 h after E2 injection. Although [125I]IGF-I binding was significantly increased per mg DNA, because of a more marked increase in membrane protein after E2, [125I]IGF-I binding, when expressed per mg membrane protein, decreased. This change in [125I]IGF-I binding resulted from a change in receptor number with no change in receptor affinity. In mature cycling rats, the proestrous uteri showed the lowest level of [125I]IGF-I binding per mg membrane protein, although because of the greater yield of protein from proestrous uteri, the total [125I]IGF-I-binding capacity of these uteri were greater than that of uteri from other stages of the estrous cycle. The lowest [125I]IGF-I binding was seen in the diestrous uteri. These studies demonstrate the presence of authentic type I IGF-I receptors in the rat uterus localized predominantly to the myometrial smooth muscle cells. In addition, E2 appears to regulate the uterine IGF-I receptor in the immature rat, and the cyclical changes in the mature rat are consistent with a role of E2 in regulation of this receptor in vivo.