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Mol Cell Endocrinol. 2015 Jan 5;399:22-31. doi: 10.1016/j.mce.2014.08.013. Epub 2014 Aug 29.

Possible involvement of glucocorticoids in 5α-dihydrotestosterone-induced PCOS-like metabolic disturbances in the rat visceral adipose tissue.

Author information

1
Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
2
Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and School of Medicine, University of Belgrade, Dr Subotića 13, Belgrade 11000, Serbia.
3
Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., Belgrade 11000, Serbia.
4
CHC Bežanijska kosa, Bežanijska kosa bb, Belgrade 11000, Serbia.
5
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.

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.

KEYWORDS:

5α-dihydrotestosterone; Glucocorticoids; Lipogenesis; PCOS; Visceral adipose tissue

PMID:
25179821
DOI:
10.1016/j.mce.2014.08.013
[Indexed for MEDLINE]

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