Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a complex reproductive disorder that is usually associated with metabolic disturbances such as obesity, dyslipidemia and insulin resistance. In this study, female rats treated with nonaromatizable 5α dihydrotestosterone (DHT) were used as an animal model of PCOS. The aim of this study was to assess the presence of inflammation in liver and visceral adipose tissue (VAT), which accompanies metabolic disturbances in animal model of PCOS. Female (21 days old) Wistar rats were treated subcutaneously with DHT pellets, while control animals received placebo pellets. Glucose, triglycerides, free fatty acids (FFA) were determined in blood plasma, while corticosterone was analyzed both in plasma and liver. Expression of genes and proteinsinvolved in lipid metabolism, such as sterol regulatory element binding protein1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), lipin-1, adipose tissue triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), were analyzed in the VAT of treated rats. Tissue inflammationevaluated by nuclear factor kappa B (NFκB)protein level and intracellular distribution, as well as by TNFα, IL6 and IL1β mRNA levels. Glucocorticoid signaling was examined at the level of 11 beta hydroxysteroid dehydrogenase type 1 (11βHSD1) and 5α-reductase, as well asby glucocorticoid receptor (GR) leveland its subcellular distribution. The results showed that DHT treatment induced increase of lipogenic factors (SREBP-1, lipin-1, FAS and PEPCK), while the level of lipolytic enzyme HSL was decreasedin VAT. These molecular alterations were accompanied by adipocyte hypertrophy, visceral obesity and elevated plasma FFA and triglyceride concentrations. Those changes in lipid metabolism were possible trigger for low-grade inflammation observed in the VAT and characterized by NFκB activation and increasedIL6 and IL1β mRNA levels. In spite of increased VAT proinflammatory mediators, the level of proinflammatory cytokines, IL6 and IL1β, was decreased in the liver of DHT-treated rats, while the activation of NFκB remained unchanged. The state of suppressed inflammation in the liver could be an outcome of stimulated glucocorticoid signaling, as judged byincreased hepatic corticosterone level and GR activation. The augmentation of hepatic glucocorticoids could be a net result of increased expression of 11βHSD1 and decreased expression of 5β-reductase mRNA. In conclusion, the results showed that abdominal obesity and dyslipidemia in the animal model of PCOS were accompanied with hypertrophic adipocytes, lipid accumulation and low-grade inflammation in the VAT. However, these metabolic disturbances did not resultin hepatic inflammation due to increased tissue levels of glucocorticoids.