الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Background: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder in premenopausal women. PCOS is frequently associated with abdominal adiposity, insulin resistance, non-alcoholic fatty liver (NAFLD) and cardiovascular risk factors. NAFLD is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Some studies had stated that high androgens level noticed in patients with PCOS leads to production of inflammatory mediators that leads to thyroid tissue destruction via apoptosis with subsequent hypothyroidism state. It has been reported that autophagy is activated in ovarian tissue of PCOS, while hepatic autophagy was enhanced in early stages but blocked at later stages of NAFLD development. Metformin is a biguanide insulin sensitizer which improves insulin action by increasing insulin sensitivity, it has been demonstrated that metformin crosses the blood-brain barrier and presents a central mechanism of TSH inhibition. Prenatally androgenized female nonhuman primates e.g: rats manifest most of the reproductive and metabolic derangements observed in women with PCOS. Aim: to study the possible beneficial effects of Metformin and Levothyroxine alone and in combination on autophagy regulation in a rat model of polycystic ovary syndrome induced non- alcoholic fatty liver disease. Methodolgy: Testosterone Enanthate was used to induce PCOS in female wistar rats by receiving testosterone enanthate subcutaneously at a dose of 7.5 mg dissolved in sesame oil by S.C. injection daily from embryonic day 16 (E16) to E19, female offsprings are divided into; control group, offspring model group, metformin treated group receiving (300 mg/kg/day) orally for 2 weeks, levothyroxine treated group receiving (50ug/kg/day) i.p for 3 weeks, and metformin+levothyroxine group. Results: Metformin+levothyroxine combination treatment had decreased body weight, liver weight, ALT, AST, serum testosterone, luteinizing hormone, increased serum estradiol level, improved insulin sensitivity and dyslipidemia, also the combination treatment restored autophagy process as compared to offspring model group. Conculsion: Combination of Metformin and Levothyroxine has beneficial effects on body weight, liver index, hormonal PCOS profile (T, LH and E2), metabolic profile (total cholesterol, TG and LDL), insulin resistance (blood glucose, serum insulin, serum c-peptide and HOMA-IR) and thyroid profile (TSH, total T3 and total T4) with restoration of hepatic and ovarian autophagy and improvement in the ovarian and hepatic histopathological pictures.