The RNA-Binding Protein ELAVL1 Regulates GnRH Receptor Expression and the Response to GnRH
| Autor: | Tae-Shin Kim, Tomohiro Terasaka, Danmei Li, Hiral Dave, Mark A. Lawson, Oscar Muñoz, Eri Terasaka, Dequina A. Nicholas, Bhakti Gangapurkar |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system medicine.drug_class Active Transport Cell Nucleus Gonadotropic cell ELAV-Like Protein 1 Gonadotropin-Releasing Hormone 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Anterior pituitary Polysome Internal medicine medicine Animals RNA Messenger Extracellular Signal-Regulated MAP Kinases Cells Cultured Research Articles Regulation of gene expression Gene knockdown Chemistry GNRHR Luteinizing Hormone Gonadotropin secretion Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Female Gonadotropin hormones hormone substitutes and hormone antagonists Receptors LHRH |
| Zdroj: | Endocrinology |
| ISSN: | 1945-7170 |
| Popis: | Gonadotropin secretion, which is elicited by GnRH stimulation of the anterior pituitary gonadotropes, is a critical feature of reproductive control and the maintenance of fertility. In addition, activation of the GnRH receptor (GnRHR) regulates transcription and translation of multiple factors that regulate the signaling response and synthesis of gonadotropins. GnRH stimulation results in a broad redistribution of mRNA between active and inactive polyribosomes within the cell, but the mechanism of redistribution is not known. The RNA-binding protein embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) binds to AU-rich elements in mRNA and is one of the most abundant mRNA-binding proteins in eukaryotic cells. It is known to serve as a core component of RNA-binding complexes that direct the fate of mRNA. In LβT2 gonadotropes, we showed that ELAVL1 binds to multiple mRNAs encoding factors that are crucial for gonadotropin synthesis and release. Association with some mRNAs is GnRH sensitive but does not correlate with abundance of binding. We also showed MAPK-dependent changes in intracellular localization of ELAVL1 in response to GnRH stimulation. Knockdown of ELAVL1 gene expression resulted in reduced Lhb and Gnrhr mRNA levels, reduced cell surface expression of GnRHR, and reduced LH secretion in response to GnRH stimulation. Overall, these observations not only support the role of ELAVL1 in GnRHR-mediated regulation of gene expression and LH secretion but also indicate that other factors may contribute to the precise fate of mRNA in response to GnRH stimulation of gonadotropes. |
| Databáze: | OpenAIRE |
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