Rutanen E M
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Gynecol Endocrinol. 1998 Dec;12(6):399-406. doi: 10.3109/09513599809012842.
Growth factors and related peptides are believed to mediate and modulate the actions of hormones at their target tissues through autocrine/paracrine mechanisms. Endometrial stromal cells produce insulin-like growth factors I and II (IGF-I and IGF-II) as well as the high-affinity IGF binding proteins (IGFBPs), whereas epithelial cells and, in a lesser amount, also stromal cells contain cell membrane receptors for IGFs. IGFs have proliferative, differentiative and metabolic effects. Estrogen stimulates IGF-I gene expression in the endometrium, and IGF-I is assumed to mediate estrogen action. IGF-II gene expression is associated with endometrial differentiation. All six high-affinity IGFBPs are expressed in human endometrium, the most abundant being IGFBP-1. This is secreted by predecidualized/decidualized endometrial stromal cells in late secretory phase endometrium and pregnancy decidua, i.e. under the action of progesterone. The primary negative regulator of IGFBP-1 expression is insulin, by inhibiting IGFBP-1 transcription. IGFBP-1 inhibits the receptor binding and biological actions of IGF-I in the endometrium and in cultured human trophoblastic cells. These findings support the view that the IGF system has autocrine and paracrine functions in the regulation of endometrial proliferation and differentiation. After implantation, decidual IGFBP-1 may regulate IGF actions at the embryo-endometrial interface, since trophoblast cells contain IGF receptors and express IGF-II, but do not express IGFBP-1. Clinical conditions that are known to increase the risk of endometrial cancer are all characterized by the absence of IGFBP-1. Thus, like unopposed estrogen, unopposed IGF-I action may also lead to uncontrolled endometrial proliferation and favor the development of endometrial cancer. The measurement of mRNAs encoding the IGF system might provide a novel tool to evaluate the endometrial response to endogenous and exogenous estrogens and progestins at the molecular level.
生长因子和相关肽被认为通过自分泌/旁分泌机制介导和调节激素在其靶组织中的作用。子宫内膜基质细胞产生胰岛素样生长因子I和II（IGF-I和IGF-II）以及高亲和力的IGF结合蛋白（IGFBPs），而上皮细胞以及少量的基质细胞含有IGF的细胞膜受体。IGF具有增殖、分化和代谢作用。雌激素刺激子宫内膜中IGF-I基因的表达，并且IGF-I被认为介导雌激素的作用。IGF-II基因的表达与子宫内膜分化有关。所有六种高亲和力的IGFBPs均在人子宫内膜中表达，其中最丰富的是IGFBP-1。它由分泌晚期子宫内膜和妊娠蜕膜中预蜕膜化/蜕膜化的子宫内膜基质细胞分泌，即在孕酮的作用下分泌。IGFBP-1表达的主要负调节因子是胰岛素，通过抑制IGFBP-1转录来实现。IGFBP-1抑制IGF-I在子宫内膜和培养的人滋养层细胞中的受体结合及生物学作用。这些发现支持了IGF系统在调节子宫内膜增殖和分化中具有自分泌和旁分泌功能的观点。着床后，蜕膜IGFBP-1可能调节胚胎-子宫内膜界面处的IGF作用，因为滋养层细胞含有IGF受体并表达IGF-II，但不表达IGFBP-1。已知增加子宫内膜癌风险的临床情况均以缺乏IGFBP-1为特征。因此，与无对抗的雌激素一样，无对抗的IGF-I作用也可能导致子宫内膜不受控制地增殖，并有利于子宫内膜癌的发展。测量编码IGF系统的mRNA可能提供一种新工具，在分子水平上评估子宫内膜对内源性和外源性雌激素及孕激素的反应。
