IGF-1 gene expression is differentially regulated by estrogen receptors α and β in mouse endometrial stromal cells and ovarian granulosa cells

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.