Expression of Insulin-Like Growth Factor-I (IGF-l) and its Receptor in the Peri-Implantation Mouse Uterus, and Cell-Specific Regulation of IGF-l Gene Expression by Estradiol and Progesterone1

Abstract

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.

Estradiol, Progesterone, and Transforming Growth Factor α Regulate Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Expression in Mouse Endometrial Cells

“…Estrogen stimulates Igf1 transcription (Murphy et al, 1987;Ghahary et al, 1990;Kapur et al, 1992;Zhou et al, 1994;Ohtsuki et al, 2005), and high levels of circulating estrogen at proestrus induced high Igf1 mRNA levels. Igf1r mRNA levels also changed during the estrous cycle; they were high at diestrus and low during proestrus and estrus, suggesting that the responsiveness of endometrial cells to IGF1 depends upon the stage of the estrous cycle, and possibly upon levels of estrogen and progestin.…”

“…The steroid hormone-induced proliferation of endometrial cells is thought to be mediated by growth factors produced in endometrial stromal cells (Tomooka et al, 1986;DiAugustine et al, 1988;Beck and Garner, 1992;Das et al, 1994;Cooke et al, 1997). Insulin-like growth factor 1 (IGF1) is expressed in all components of the mouse uterus and its expression is regulated by estrogen (Murphy et al, 1987;Ghahary et al, 1990;Kapur et al, 1992;Ohtsuki et al, 2007). Moreover, IGF1 promotes the proliferation of endometrial cells (Shiraga et al, 1997;Sato et al, 2002;Inoue et al, 2005;Zhu et al, 2007).…”

Influence of maternal environment on the number of transferable embryos obtained in response to superovulatory FSH treatments in ewes

“…Moreover, delays or deficiencies in progesterone release also affected the viability of the recovered embryos. Prior authors have described the role of both hormones, oestradiol and progesterone, on the expression of several growth factors, mainly IGF on the oviduct and uterine secretions [34][35][36][37]. Although there are no studies on superovulated ewes, the presence of IGF and its binding proteins during the early embryo development, from 1 cell to the blastocyst, suggests an important role of these peptides [38][39][40].…”

Effect of diethylstilbestrol on cell proliferation and expression of epidermal growth factor in the developing female rat reproductive tract

“…EGF and insulin-like growth factor (IGF)-I stimulate cell proliferation in immature mouse uterine and vaginal epithelial cells in vitro (Tomooka et al 1986, Iguchi et al 1987, Shiraga et al 1997. Because estrogen stimulates uterine epithelial cell proliferation (McCormack & Glasser 1980, Quarmby & Korach 1984 and expression of EGF, IGF-I, heparin-binding EGF-like growth factor, transforming growth factor (TGF)-and EGF-R in the reproductive tracts of mice and rats, these growth factors may mediate the estrogen-induced proliferative and differentiative responses in rodent reproductive tracts (Murphy et al 1987, DiAugustine et al 1988, Nelson et al 1991, Beck & Garner 1992, Ignar-Trowbridge et al 1992, Kapur et al 1992, Das et al 1994, Sahlin et al 1994, Zhang et al 1994, Falck & Forsberg 1996, Hom et al 1998. In the fetal reproductive tract, expression of EGF-R in mice (Bossert et al 1990), and EGF, TGFand IGF-I in rats (Koike & Noumura 1993, Kanno et al 1994, Gu et al 1999) was reported.…”