Effects of metformin and physical activity on the hypothalamus, pituitary and ovary of rat model of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women in reproductive age. Metformin and physical exercise are commonly prescribed for PCOS treatment; however their action mechanisms are not fully understood. In this sense, the using of animal models may help in the better understanding of therapeutic strategies and PCOS pathophysiology. The aim of this study is to analyze the effects of metformin and physical exercise on hypothalamus, pituitary and ovary in animal model of PCOS induced by subcutaneous injection of testosterone propionate (1.25 mg) between 0-3 days of age. Control animals will receive only vehicle injection in the same period. Will be utilized 42 female rats equally sorted in 6 groups: control group + placebo treatment (GI), control group + physical exercise + treatment with placebo (GII), PCOS group + treatment with placebo (GIII), PCOS group + treatment with metformin (GIV), PCOS group + physical exercise + treatment with placebo (GV) and PCOS group + physical exercise + treatment with metformin (GVI). Treatment with placebo, metformin and/or physical exercise will be realized from 90 to 130 days of life. At 130 days, the animals will be euthanized and, posteriorly, hypothalamus, pituitary, ovary and blood will be collected. Will be evaluated the gene and protein expression of important ligands and receptors to reproductive physiology in hypothalamus and pituitary, such as GnRH, Kisspeptin, Dynorphin A, Neurokinin B, ²-endorphin, opioid receptor mu, insulin receptor, OCT-1 and OCT-3, in hypothalamus, and GnRH receptor, ²-endorphin, OCT-1 and OCT-3, in pituitary, that have been credited to PCOS. Ovary will be analyzed by histomorphometry to corpora lutea counting and the blood will be utilized to dosage of LH, testosterone, insulin and glucose serum levels. (AU)