doiSerbia

5α-dihydrotestosterone treatment induces metabolic changes associated with polycystic ovary syndrome without interfering with hypothalamic leptin and glucocorticoid signaling

Nikolić Marina (Institute for Biological Research “Siniša Stanković”, Department of Biochemistry, Belgrade)
Veličković Nataša (Institute for Biological Research “Siniša Stanković”, Department of Biochemistry, Belgrade)
Đorđević Ana (Institute for Biological Research “Siniša Stanković”, Department of Biochemistry, Belgrade)
Bursać Biljana (Institute for Biological Research “Siniša Stanković”, Department of Biochemistry, Belgrade)
Macut Đuro (Clinical Center of Serbia and School of Medicine, Institute of Endocrinology, Diabetes and Metabolic Diseases, Belgrade)
Božić-Antić Ivana (Clinical Center of Serbia and School of Medicine, Institute of Endocrinology, Diabetes and Metabolic Diseases, Belgrade)
Bjekić-Macut Jelica (CHC Bežanijska kosa, Belgrade)
Matić Gordana (Institute for Biological Research “Siniša Stanković”, Department of Biochemistry, Belgrade)
Vojnović-Milutinović Danijela (Institute for Biological Research “Siniša Stanković”, Department of Biochemistry, Belgrade)

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogenous disorder, with hyperandrogenism, chronic anovulation and polycystic ovaries as basic characteristics, and associated metabolic syndrome features. Increased secretion of leptin and leptin resistance are common consequences of obesity. Leptin is a hormone with anorexigenic effects in the hypothalamus. Its function in the regulation of energy intake and consumption is antagonized by glucocorticoids. By modulating leptin signaling and inflammatory processes in the hypothalamus, glucocorticoids can contribute to the development of metabolic disturbances associated with central energy disbalance. The aim of the study was to examine the relationship between hypothalamic leptin, glucocorticoid and inflammatory signaling in the development of metabolic disturbances associated with PCOS. The study was conducted on an animal model of PCOS generated by a continual, 90-day treatment of female rats with 5α-dihydrotestosterone (DHT). The model exhibited all key reproductive and metabolic features of the syndrome. mRNA and/or protein levels of the key components of hypothalamic glucocorticoid, leptin and inflammatory pathways, presumably contributing to energy disbalance in DHT-treated female rats, were measured. The results indicated that DHT treatment led to the development of hyperphagia and hyperleptinemia as metabolic features associated with PCOS. However, these metabolic disturbances could not be ascribed to changes in hypothalamic leptin, glucocorticoid or inflammatory signaling pathways in DHT-treated rats.

Keywords: DHT, hypothalamus, leptin, glucocorticoids, inflammation

Projekat Ministarstva nauke Republike Srbije, br. III41009