Mechanistic target of rapamycin (MTOR) signaling during ovulation in mice
| Autor: | Dayananda Siddappa, Vilceu Bordignon, Anitha Kalaiselvanraja, Raj Duggavathi, Philippe P. Roux, Bernardo Garziera Gasperin, Lisa Dupuis |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
endocrine system medicine.medical_specialty RPTOR P70-S6 Kinase 1 Cell Biology Biology medicine.anatomical_structure Endocrinology Internal medicine Genetics medicine biology.protein Kinase activity Protein kinase A Corpus luteum Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Developmental Biology |
| Zdroj: | Molecular Reproduction and Development. 81:655-665 |
| ISSN: | 1040-452X |
| Popis: | SUMMARY A complex network of endocrine/paracrine signals regulates granulosa-cell function inovarianfollicles.Mechanistictargetofrapamycin(MTOR)hasrecentlyemergedas a master intracellular integrator of extracellular signals and nutrient availability. The objectives of the present study were to characterize the expression pattern and kinase activity of MTOR during follicular and corpus luteum development, and to examine how inhibition of MTOR kinase activity affects preovulatory maturation of ovarian follicles. MTOR expression was constitutive throughout follicular and corpus luteum development. Gonadotropins induced MTOR kinase activity in the ovary, which was inhibited by rapamycin treatment (10mg/g body weight, intraperitoneal injection). Inhibition of human chorionic gonadotropin (hCG)-induced MTOR activity during preovulatory follicle maturation did not change key events of ovulation. Granulosa cells of rapamycin-treated mice showed reduced MTOR kinase activity at 1 and 4hr post-hCG and overexpression of hCG-induced ovulation genes at 4hr post-hCG. Overexpression of these ovulatory genes was associated with hyperactivation of extracellular signal-regulated kinase 1/2 (ERK1/2), which occurred in response to inhibition of MTOR with rapamycin and suggested that MTOR may function as a negative regulator of the mitogen-activated protein kinase (MAPK) pathway. Indeed, simultaneous inhibition of MTOR and ERK1/2 activities during preovulatory follicle maturation caused anovulation. Inhibition of hCG-induced ERK1/2 activity alone suppressed MTOR kinase activity, indicating that MAPK pathway is upstream of MTOR. Thus, normal ovulation appears to be a result of complex interactions between MTOR and MAPK signaling pathways in granulosa cells of ovulating follicles in mice. |
| Databáze: | OpenAIRE |
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