Melatonin attenuates glucocorticoid effect induced by medroxyprogesterone acetate in rats

Medroxyprogesterone acetate (MPA) acts on glucocorticoid receptors and, when it is in excess, can cause clinical disorders comparable to hyperadrenocorticism. Melatonin (MEL) is a hormone with potent antioxidant and anti-glucocorticoid activity and it can be beneficial in the excessive activation of glucocorticoid receptors. To evaluate the protective effects of MEL on the glucocorticoid effect of MPA, 34 male Wistar rats were randomized into four groups: CON (control), MEL, MPA, and MPA + MEL. The animals were treated for 28 days, by subcutaneous injection. At the high dose that we used, the MPA caused effects compatible with an excessive activation of glucocorticoid receptors, resulting on a reduction in adrenal size, less weight gain, lower final body weight and feeding efficiency, and fewer lymphocytes compared with the control group. In addition, there was an increase in abdominal fat, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, erythrocytes, hemoglobin, hematocrit, and hepatic vacuolization. We concluded that MEL was effective reducing the mean values of total cholesterol, high-density lipoprotein (HDL), urea, VLDL, triglycerides, hepatic microvacuolization and abdominal fat/weight in rats treated with MPA. These findings indicate that MEL attenuates the harmful effects of MPA.