Giudice L C, Dsupin B A, Jin I H, Vu T H, Hoffman A R
Department of Gynecology and Obstetrics, Stanford University Medical Center, California 94305.
J Clin Endocrinol Metab. 1993 May;76(5):1115-22. doi: 10.1210/jcem.76.5.8496300.
During the menstrual cycle, the endometrium undergoes characteristic changes in response to circulating sex steroids. Intense mitotic activity of glands and stroma occurs in the proliferative (estradiol-dominant) phase, and glandular secretion and stromal differentiation in the secretory (progesterone-dominant) phase. The insulin-like growth factors (IGF-I and IGF-II) promote cellular growth and differentiation and have been proposed to participate in these cyclic endometrial events, acting as mediators of steroid hormones. The objective of this study was to determine whether the messenger RNAs (mRNAs) encoding the IGF peptides and the type I and type II IGF receptors are differentially expressed in human endometrium during the menstrual cycle and in early pregnancy. A solution hybridization ribonuclease protection assay, using 32P-labeled riboprobes for IGF-I, IGF-II, and beta-actin (control), revealed IGF-I gene expression primarily in proliferative and early secretory endometrium and abundant IGF-II gene expression in mid-late secretory endometrium and early pregnancy decidua. Northern analysis, using IGF-I and IGF-II complementary DNA probes, revealed multiple IGF-I mRNAs [2-7.6 kilobase (kb)], expressed primarily in proliferative and early secretory endometrium, and IGF-II mRNAs (1.4-6.0 kb), expressed primarily in secretory endometrium and in early pregnancy decidua. The 7.6-kb IGF-I mRNA and the 6.0-kb IGF-II mRNA were most abundantly expressed. IGF-IEa and IGF-IEb mRNA splicing variants were present in a ratio of about 9:1, respectively. Type I and type II IGF receptor gene expression in endometrium was investigated using specific riboprobes and the ribonuclease protection assay. Messenger RNAs encoding both receptors were more abundantly expressed in the secretory phase and during early pregnancy, compared to the proliferative phase. These results show that mRNAs encoding the IGF peptides and their receptors are differentially expressed in human endometrium, depending on the steroid hormone milieu. The preferential expression of IGF-I mRNA in the proliferative phase supports the hypothesis that IGF-I is an estromedin in human endometrium. The expression of endometrial IGF-II mRNA in the mid to late secretory phase and in early pregnancy supports a role for IGF-II in differentiative functions of the endometrium, perhaps including endometrial tissue shedding in the menstrual cycle or remodeling during early pregnancy.
在月经周期中，子宫内膜会因循环中的性类固醇而发生特征性变化。在增殖期（以雌二醇为主），腺体和基质会出现强烈的有丝分裂活动；在分泌期（以孕酮为主），则会出现腺体分泌和基质分化。胰岛素样生长因子（IGF-I和IGF-II）可促进细胞生长和分化，并被认为参与了这些周期性的子宫内膜事件，充当类固醇激素的介质。本研究的目的是确定编码IGF肽以及I型和II型IGF受体的信使核糖核酸（mRNA）在月经周期和妊娠早期的人子宫内膜中是否存在差异表达。使用针对IGF-I、IGF-II和β-肌动蛋白（对照）的32P标记核糖探针进行溶液杂交核糖核酸酶保护分析，结果显示IGF-I基因主要在增殖期和分泌早期的子宫内膜中表达，而IGF-II基因在分泌中期至晚期的子宫内膜和妊娠早期的蜕膜中大量表达。使用IGF-I和IGF-II互补DNA探针进行的Northern分析显示，存在多种IGF-I mRNA[2 - 7.6千碱基（kb）]，主要在增殖期和分泌早期的子宫内膜中表达；以及IGF-II mRNA（1.4 - 6.0 kb），主要在分泌期的子宫内膜和妊娠早期的蜕膜中表达。7.6 kb的IGF-I mRNA和6.0 kb的IGF-II mRNA表达最为丰富。IGF-IEa和IGF-IEb mRNA剪接变体的比例分别约为9:1。使用特异性核糖探针和核糖核酸酶保护分析研究了子宫内膜中I型和II型IGF受体基因的表达。与增殖期相比，编码这两种受体的mRNA在分泌期和妊娠早期表达更为丰富。这些结果表明，编码IGF肽及其受体的mRNA在人子宫内膜中存在差异表达，这取决于类固醇激素环境。IGF-I mRNA在增殖期的优先表达支持了IGF-I是人类子宫内膜中一种雌激素介质的假说。子宫内膜IGF-II mRNA在分泌中期至晚期以及妊娠早期表达，这支持了IGF-II在子宫内膜分化功能中的作用，可能包括月经周期中的子宫内膜组织脱落或妊娠早期的重塑。
