Alternative Leader-Exon Usage in Mouse IGF-I mRNA Variants: Class 1 and Class 2 IGF-I mRNAs

Abstract

The mouse IGF-I gene contains six exons, and exon 1 and exon 2 gene are considered to be leader exons. The regulatory mechanism of alternative usage of the leader exons is unclear in mice. The present study was aimed at clarifying changes in class 1 (derived from exon 1) and class 2 (derived from exon 2) IGF-I mRNA expression in mice under various conditions. Both class 1 and class 2 IGF-I mRNAs were expressed in the mouse uterus, liver and kidney, and class 1 IGF-I mRNA was the major transcript in all organs studied. In the uterus, both class 1 and class 2 IGF-I mRNA expression changed markedly during the estrous cycle, with the highest level at proestrus, but in the liver and kidney there were no significant changes in IGF-I mRNA expression during the estrous cycle. Estrogen treatment increased both class 1 and class 2 IGF-I mRNA levels in the uterus of ovariectomized mice, but class 1 mRNA expression increased more in response to estrogen treatment than class 2 mRNA expression. These findings suggest that estrogen stimulates IGF-I gene expression in uterine cells, and that a promoter involved in transcription of class 1 IGF-I mRNA is more responsive to estrogen. In conclusion, the present study revealed that two leader exons of mouse IGF-I gene are used in the uterus, liver and kidney. IGF-I mRNA levels of both classes changed during the estrous cycle in the uterus, but not in the liver or kidney. Estrogen increased IGF-I mRNA levels of both classes in the uterus.

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

“…Igf1 mRNA levels changed during the estrous cycle, which was consistent with our previous report (Ohtsuki et al, 2007). 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.…”

“…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).…”

Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload

“…We therefore analyzed expression of class 2 mRNA as the major Igf1 transcript in the heart and cardiac fibroblasts ( Figure 6, A-C). Igf1 class 1 and class 2 cDNA fragments were amplified using a forward primer specific for each leader exon (exon 1, 5′-ATGGGGAAAATCAGCAGTC-3′; exon 2, 5′-CTGCCTGT-GTAAACGACCCGG-3′) and a reverse primer (exon 3-4 junction, 5′-GGCT-GCTTTTGTAGGCTTCAGTGG-3′) (56).…”

Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH

“…The IGF-I gene can be spliced both at the 5 0 and 3 0 ends. At the 5 0 end Class 1 or Class 2 IGF-I transcripts result depending upon their initiation from either promoter 1 (adjacent to exon 1) or 2 (adjacent to exon 2), respectively [4][5][6]. At the 3 0 end alternative splicing may result in three E domain peptides IGF-IEa, IGF-IEb and IGF-I Ec (MGF) [7][8][9].…”