5α-dihydrotestosterone treatment induces metabolic changes associated with Polycystic ovary syndrome without interfering with hypothalamic leptin and glucocorticoid signaling
2016
Authors:
Radovanović, MarinaVeličković, Nataša
Đorđević, Ana
Bursać, Biljana
Macut, Đuro
Božić Antić, Ivana
Bjekić Macut, Jelica
Matić, Gordana
Vojnović-Milutinović, Danijela
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
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; inflammationSource:
Archives of Biological Sciences, 2016, 68, 3, 473-481Funding / projects:
- Role of steroid hormones in neuroendocrine adaptation to stress and pathophysiology of metabolic syndrome - molecular mechanisms and clinical implications (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41009)
DOI: 10.2298/ABS151214001N
ISSN: 0354-4664