Kapur S, Tamada H, Dey S K, Andrews G K
Department of Obstetrics and Gynecology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.
Biol Reprod. 1992 Feb;46(2):208-19. doi: 10.1095/biolreprod46.2.208.
This study describes the expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) genes in the mouse uterus during the peri-implantation period (Days 1-6 of pregnancy), as well as effects of estradiol (E) and progesterone (P) on cell-specific IGF-I gene expression in the uterus of the ovariectomized adult mouse. Northern blot analysis showed that IGF-I mRNA levels were low but readily detectable in the uterus on Day 1 of pregnancy and steadily increased, reaching high levels just before (Day 4) and after initiation of implantation (Days 5 and 6). In general, IGF-IR transcripts were present in low abundance in uterine RNA throughout the peri-implantation period. However, six sizes of uterine IGF-IR transcripts were detected, and the relative abundance of two of these transcripts varied significantly during the peri-implantation period. Cell-specific expression of the IGF-I gene was examined by in situ hybridization to mRNA and immunohistochemical detection of protein. The results indicated that the synthesis of IGF-I on Days 1 and 2 was most predominant in glandular and luminal epithelial cells. However, on Days 3 and 4, stromal cells, and on Days 5 and 6, decidual cells appeared to be the predominant sites of synthesis of this growth factor. Uterine IGF-I gene expression was stimulated by ovarian steroids. Northern blot analysis showed that IGF-I transcripts were rare in the ovariectomized adult mouse uterus, but an injection of P and/or E caused a rapid accumulation of these transcripts. Analysis of the cell-specific expression of uterine IGF-I showed that E induced IGF-I gene expression primarily in epithelial cells, whereas P did so in the stroma. Superimposition of E on the P-primed uterus further stimulated IGF-I expression in the stroma. The results of these studies are consistent with an autocrine/paracrine function of uterine IGF-I, and indicate that ovarian steroids regulate the cell-specific and temporal patterns of expression of this gene in the peri-implantation mouse uterus.
本研究描述了胰岛素样生长因子-I（IGF-I）及其受体（IGF-IR）基因在小鼠围植入期（妊娠第1 - 6天）子宫中的表达情况，以及雌二醇（E）和孕酮（P）对成年去卵巢小鼠子宫中细胞特异性IGF-I基因表达的影响。Northern印迹分析显示，妊娠第1天时子宫中IGF-I mRNA水平较低但仍可检测到，随后稳步上升，在植入前（第4天）和植入开始后（第5天和第6天）达到高水平。一般来说，在整个围植入期，子宫RNA中IGF-IR转录本的丰度较低。然而，检测到六种大小的子宫IGF-IR转录本，其中两种转录本的相对丰度在围植入期有显著变化。通过mRNA原位杂交和蛋白质免疫组化检测来研究IGF-I基因的细胞特异性表达。结果表明，第1天和第2天IGF-I的合成在腺上皮和腔上皮细胞中最为显著。然而，在第3天和第4天，基质细胞，以及在第5天和第6天，蜕膜细胞似乎是这种生长因子合成的主要部位。卵巢类固醇刺激子宫IGF-I基因表达。Northern印迹分析显示，在成年去卵巢小鼠子宫中IGF-I转录本很少见，但注射P和/或E会导致这些转录本迅速积累。对子宫IGF-I细胞特异性表达的分析表明，E主要在上皮细胞中诱导IGF-I基因表达，而P则在基质中诱导表达。在P预处理的子宫上叠加E进一步刺激了基质中IGF-I的表达。这些研究结果与子宫IGF-I的自分泌/旁分泌功能一致，并表明卵巢类固醇调节围植入期小鼠子宫中该基因的细胞特异性和时间表达模式。
