Insulin Augments Gonadotropin-Releasing Hormone Induction of Translation in LβT2 Cells
| Autor: | Hyunjin Song, Brian D. Cherrington, Amy M. Navratil, Mark A. Lawson, Janine M. Low, Minh-Ha Do, Jeniffer B. Hernandez, Sharon J. Santos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
RNA Caps
medicine.medical_specialty Growth-hormone-releasing hormone receptor Gonadotropin-releasing hormone Gonadotrophs Caveolae Biochemistry Article Cell Line Gonadotropin-Releasing Hormone Mice Endocrinology Membrane Microdomains Internal medicine Insulin receptor substrate medicine Animals Insulin Protein Isoforms Phosphorylation Extracellular Signal-Regulated MAP Kinases Molecular Biology Protein kinase B Insulin-like growth factor 1 receptor biology Akt/PKB signaling pathway IRS2 Receptor Insulin Cell biology Enzyme Activation Mice Inbred C57BL Insulin receptor Cholesterol Protein Biosynthesis biology.protein Proto-Oncogene Proteins c-akt |
| Popis: | The integrated signaling of insulin and gonadotropin-releasing hormone in the pituitary gonadotropes may have a profound bearing on reproductive function, although the cross-receptor signaling mechanisms are unclear. We demonstrate that the insulin receptor is constitutively localized to non-caveolar lipid raft microdomains in the pituitary gonadotrope cell line LbetaT2. The localization to rafts is consistent with similar localization of the GnRH receptor. Insulin receptor phosphorylation occurs in raft domains and activates the downstream signaling targets Insulin Receptor Substrate1 and Akt/Protein Kinase B. Although insulin alone does not strongly activate the extracellular signal-regulated kinase second messenger cascade, co-stimulation potentiates the phosphorylation of the extracellular signal-regulated kinase by gonadotropin-releasing hormone. The co-stimulatory effect of insulin and gonadotropin-releasing hormone is also evident in increased activation of cap-dependent translation. In contrast, co-stimulation attenuates Akt/Protein Kinase B activation. Our results show that both gonadotropin-releasing hormone and insulin are capable of mutually altering their respective regulatory signaling cascades. We suggest that this provides a mechanism to integrate neuropeptide and energy homeostatic signals to modulate reproductive function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|