Mineralocorticoid receptor (MR) activation is involved in the pathogenesis of main components of metabolic syndrome. Combined estrogen – progestin oral contraceptives (COC), used by tens of millions of women in the world, have been associated with increased cardiometabolic risk factors. Although possible underlying mechanisms by which COC induces these risk factors have not been well elucidated. We therefore hypothesized that abnormal lipid profile and pancreatic β-cell function caused by treatment with COC steroids containing levonorgestrel and ethinylestradiol is through MR activation.Design and Method:
Female Wistar rats were randomly allotted into four groups, receiving (p.o.) vehicle, COC (5.0 μg levonorgestrel and 1.0 μg ethinylestradiol) with or without MR antagonist, spironolactone (0.5 mg/kg) daily for 8 weeks. Insulin resistance (IR) and pancreatic β-cell function were estimated using the homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) and β-cell (HOMA-β) respectively. Dyslipidemia was evaluated by atherogenic lipids; triglyceride (TG)/HDL-cholesterol and total cholesterol (TC)/HDL-cholesterol ratios. Circulating profibrotic markers, plasminogen activator inhibitor – 1 (PAI-1) and glycogen synthase kinase-3 (GSK-3) were estimated by ELISA.Results:
Results showed that COC treatment led to increase in HOMA-IR, HOMA-β, TC/HDL-cholesterol, TG/HDL-cholesterol, PAI-1 and GSK-3. On the other hand COC treatment caused impaired glucose tolerance. However the MR antagonist ameliorated these effects except HOMA-IR and impaired glucose tolerance.Conclusions:
The result from the present study showed that COC treatment leads to abnormal atherogenic lipid and pancreatic β-cell function, which are associated with elevated circulating PAI-1 and GSK-3. The result also implies that activation of MR is probably involved in COC – induced cardiometabolic effects and reduction of PAI-1 and GSK-3 may be useful therapeutic approach for the treatment of COC – induced cardiometabolic disorders.