| First Author | Hewitt SC | Year | 2017 |
| Journal | Endocrinology | Volume | 158 |
| Issue | 8 | Pages | 2427-2435 |
| PubMed ID | 28586424 | Mgi Jnum | J:248189 |
| Mgi Id | MGI:5916894 | Doi | 10.1210/en.2017-00349 |
| Citation | Hewitt SC, et al. (2017) Role of ERalpha in Mediating Female Uterine Transcriptional Responses to IGF1. Endocrinology 158(8):2427-2435 |
| abstractText | Estrogen (E2) signaling through its nuclear receptor, E2 receptor alpha (ERalpha) increases insulinlike growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor. Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERalpha-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERalpha in mediating the IGF1 transcriptional vs growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ERalphaUtcKO) mice, which selectively lack ERalpha in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ERalpha expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ERalpha binding sites in uterine chromatin using chromatin immunoprecipitation sequencing. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ERalpha-mediated and ERalpha-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife. |
