Ghahary A, Murphy L J
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Endocrinology. 1989 Aug;125(2):597-604. doi: 10.1210/endo-125-2-597.
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.
本研究旨在鉴定子宫胰岛素样生长因子-I（IGF-I）受体，并研究在整个发情周期以及对未成熟大鼠给予17β-雌二醇（E2）后这些受体的调节情况。我们通过结合和交联实验在子宫粗膜中证实了I型IGF受体。子宫IGF-I受体的特性与其他组织报道的相似，具有高亲和力成分（Kd = 0.12 nM；结合容量 = 0.028 pmol/mg蛋白质）和低亲和力成分（Kd = 0.98 nM；结合容量 = 0.041 pmol/mg蛋白质）。[125I]IGF-I与子宫切片结合的放射自显影显示，IGF-I受体定位于子宫肌层的平滑肌细胞，外纵层的IGF-I受体密度高于内环层。在未成熟大鼠中，早在E2注射后6小时，给予E2就显著增加了每个子宫的总[125I]IGF-I结合量。尽管每毫克DNA的[125I]IGF-I结合量显著增加，但由于E2后膜蛋白增加更为明显，每毫克膜蛋白的[125I]IGF-I结合量下降。[125I]IGF-I结合的这种变化是由于受体数量的改变，而受体亲和力没有变化。在成熟的周期性发情大鼠中，动情前期子宫每毫克膜蛋白的[125I]IGF-I结合水平最低，尽管由于动情前期子宫蛋白质产量更高，这些子宫的总[125I]IGF-I结合能力大于发情周期其他阶段的子宫。在间情期子宫中观察到最低的[125I]IGF-I结合。这些研究证明大鼠子宫中存在真正的I型IGF-I受体，主要定位于肌层平滑肌细胞。此外，E2似乎在未成熟大鼠中调节子宫IGF-I受体，成熟大鼠中的周期性变化与E2在体内调节该受体的作用一致。
