Letrozole Rat Model Mimics Human Polycystic Ovarian Syndrome and Changes in Insulin Signal Pathways
| Autor: | Lishan Huang, Jun-Xin Zhang, Juan Yang, Jingjing Dun, Qiu-Ping Lin, Lin Ying, Xiumi You, Jin-Bang Xu, Feng Ji, Mingqing Huang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Estrous Cycle 030204 cardiovascular system & hematology Diet High-Fat Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Insulin resistance Internal medicine Animals Insulin Medicine Obesity Protein kinase B biology business.industry Animal Study Letrozole Body Weight Ovary nutritional and metabolic diseases General Medicine Lipid Metabolism medicine.disease Lipids Polycystic ovary Rats Disease Models Animal Insulin receptor Endocrinology 030220 oncology & carcinogenesis Models Animal biology.protein Female Insulin Resistance business Polycystic Ovary Syndrome Signal Transduction medicine.drug Compensatory Hyperinsulinemia Hormone |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| DOI: | 10.12659/msm.923073 |
| Popis: | BACKGROUND The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with all reproductive and metabolic phenotypes in a rat model. MATERIAL AND METHODS Twenty-four 3-week-old female Sprague-Dawley rats were randomized into 4 groups: control, Letrozole, HFD, and Letrozol+HFD. The PCOS model was induced by 12 weeks of Letrozole treatment (1 mg/kg p.o. dissolved in 0.5% CMC solutions once daily) and HFD. Ovarian morphology, estrous cyclicity, hormonal status, body weight, glucose and insulin tolerance, lipid profile, and insulin signaling pathway were investigated. RESULTS The rat model manifests anovulatory cycles and PCO morphology, increased body weight, elevated testosterone levels, abnormal glucose and lipid metabolism, and insulin resistance. The rat model also expresses significantly decreased phosphorylation of 6 essential signaling proteins - INSR, IRS, PI3K, AKT, ERK1, ERK2 - in the PI3K/AKT and MAPK/ERK pathways in the classic insulin-sensitive tissues (e.g., quadriceps femoris muscle, omentum majus, and liver), as well as non-classic target ovary tissues. Disrupted insulin signaling contributes to the decrease in insulin sensitivity and compensatory hyperinsulinemia in PCOS rats. CONCLUSIONS Continuous administration of letrozole and high-fat diets can induce PCOS, metabolic phenotypes, and disrupted activation of the insulin signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|