title: Possible involvement of glucocorticoids in 5α-dihydrotestosterone-induced PCOS-like metabolic disturbances in the rat visceral adipose tissue.
abstract: Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, visceral obesity and insulin resistance. We hypothesized that changes in glucocorticoid metabolism and signaling in the visceral adipose tissue may contribute to disturbances of lipid metabolism in the rat model of PCOS obtained by 5α-dihydrotestosterone (DHT) treatment of prepubertal female Wistar rats. The results confirmed that DHT treatment caused anovulation, obesity and dyslipidemia. Enhanced glucocorticoid prereceptor metabolism, assessed by elevated intracellular corticosterone and increased 11 beta-hydroxysteroid dehydrogenase type 1 mRNA and protein levels, was accompanied by glucocorticoid receptor (GR) nuclear accumulation. In concert with the increased expression of GR-regulated prolipogenic genes (lipin-1, sterol regulatory element binding protein 1, fatty acid synthase, phosphoenolpyruvate carboxykinase), histological analyses revealed hypertrophic adipocytes. The results suggest that glucocorticoids influence lipid metabolism in the visceral adipose tissue in the way that may contribute to pathogenesis of metabolic disturbances associated with PCOS.
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Nikolić
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and School of Medicine, University of Belgrade, Dr Subotića 13, Belgrade 11000, Serbia.
authors.forename: Djuro
authors.initials: D
authors.lastname: Macut
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Djordjevic
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Veličković
authors.affiliation: Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Nestorović
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Bursać
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and School of Medicine, University of Belgrade, Dr Subotića 13, Belgrade 11000, Serbia.
authors.forename: Ivana Božić
authors.initials: IB
authors.lastname: Antić
authors.affiliation: CHC Bežanijska kosa, Bežanijska kosa bb, Belgrade 11000, Serbia.
authors.forename: Jelica Bjekić
authors.initials: JB
authors.lastname: Macut
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Matić
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia. Electronic address: dvojnovic@ibiss.bg.ac.rs.
authors.forename: Danijela
authors.initials: D
authors.lastname: Vojnović Milutinović
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000728:Androgens / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D013196:Dihydrotestosterone / Q000009:adverse effects* / Q000494:pharmacology; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000096:biosynthesis; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis
chemical_list: D000728:Androgens; D005938:Glucocorticoids; C530902:Lpin1 protein, rat; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D013196:Dihydrotestosterone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D054890:Fatty Acid Synthase, Type I; D019764:Phosphoenolpyruvate Carboxykinase (ATP)
keywords: 5α-dihydrotestosterone; Glucocorticoids; Lipogenesis; PCOS; Visceral adipose tissue