Ogo Yuki, Taniuchi Shusuke, Ojima Fumiya, Hayashi Sayo, Murakami Itsuo, Saito Yuka, Takeuchi Sakae, Kudo Toshiyuki, Takahashi Sumio
Department of Biology, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
J Reprod Dev. 2014;60(3):216-23. doi: 10.1262/jrd.2013-085. Epub 2014 Mar 25.
Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive functions in rats and mice. IGF-1 expression is regulated by estrogen in several reproductive organs including the uterus and ovary. Two types of estrogen receptor (ERα and ERβ) are expressed in mouse uteri and ovaries, and it is unclear whether they differently mediate IGF-1 gene transcription. To clarify the roles of ERα and ERβ, mouse endometrial stromal cells and ovarian granulosa cells were treated with ligands specific for individual estrogen receptors. In endometrial stromal cells, propyl-pyrazole-triol (PPT; ERα-selective agonist) increased Igf1 mRNA expression, which was suppressed by methyl-piperidino-pyrazole (MPP, ERα-selective antagonist), while diarylpropionitrile (DPN, ERβ-potency selective agonist) increased Igf1 mRNA expression, which was inhibited by MPP but not by 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-3-yl]phenol (PHTPP; ERβ antagonist). PHTPP enhanced the DPN-induced increase in Igf1 mRNA expression. In ovarian granulosa cells, E2 and DPN decreased Igf1 mRNA expression, whereas PPT did not affect Igf1 mRNA levels. In these cells, PHTPP inhibited the DPN-induced decrease in Igf1 mRNA expression. These results suggest that ERα facilitates Igf1 transcription, whereas ERβ appears to inhibit Igf1 gene transcription in mouse endometrial stromal cells and ovarian granulosa cells.
胰岛素样生长因子1（IGF-1）参与大鼠和小鼠生殖功能的调节。IGF-1的表达在包括子宫和卵巢在内的多个生殖器官中受雌激素调控。两种类型的雌激素受体（ERα和ERβ）在小鼠子宫和卵巢中表达，目前尚不清楚它们是否以不同方式介导IGF-1基因转录。为了阐明ERα和ERβ的作用，用针对单个雌激素受体的配体处理小鼠子宫内膜基质细胞和卵巢颗粒细胞。在子宫内膜基质细胞中，丙基吡唑三醇（PPT；ERα选择性激动剂）增加Igf1 mRNA表达，该表达被甲基哌啶基吡唑（MPP，ERα选择性拮抗剂）抑制，而二芳基丙腈（DPN，ERβ强效选择性激动剂）增加Igf1 mRNA表达，该表达被MPP抑制，但不被4-[2-苯基-5,7-双（三氟甲基）吡唑并[1,5-α]嘧啶-3-基]苯酚（PHTPP；ERβ拮抗剂）抑制。PHTPP增强了DPN诱导的Igf1 mRNA表达增加。在卵巢颗粒细胞中，E2和DPN降低Igf1 mRNA表达，而PPT不影响Igf1 mRNA水平。在这些细胞中，PHTPP抑制DPN诱导的Igf1 mRNA表达降低。这些结果表明，在小鼠子宫内膜基质细胞和卵巢颗粒细胞中，ERα促进Igf1转录，而ERβ似乎抑制Igf1基因转录。
