Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome.
Endocrine
; 72(2): 562-572, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33449293
ABSTRACT
PURPOSE:
Polycystic ovary syndrome (PCOS) is a complex reproductive disorder often associated with obesity, insulin resistance, and dyslipidemia. Hormonal changes in PCOS may also include altered glucocorticoid signaling. Our aim was to examine whether alterations in hepatic glucocorticoid signaling are associated with disturbances of glucose and lipid metabolism in animal model of PCOS.METHODS:
Female rats, 3 weeks old, were subcutaneously implanted with 5α-dihydrotestosterone (DHT) or placebo pellets for 90 days to induce PCOS. Expression of 11ß-hydroxysteroid dehydrogenase 1 (11ßHSD1) and A-ring reductases (5α and 5ß), as well as intracellular distribution of glucocorticoid receptor (GR) and expression of its regulated genes were examined in the liver. Proteins of hepatic lipid and carbohydrate metabolism and markers of inflammation were also assessed.RESULTS:
DHT treatment induced increase in body and liver mass, as well as in triglycerides and free fatty acids levels in plasma. Elevation of 11ßHSD1 and reduction of 5α-reductase expression was observed together with increased hepatic corticosterone concentration and nuclear GR activation. Induced expression of Krüppel-like factor 15 and decreased expression of genes for proinflammatory cytokines and de novo lipogenesis (DNL) were detected in the liver of DHT-treated rats, while DNL regulators and proinflammatory markers were not changed. However, increased mRNA levels of stearoyl-CoA desaturase and apolipoprotein B were observed in DHT animals.CONCLUSIONS:
DHT treatment stimulated hepatic glucocorticoid prereceptor metabolism through increased corticosterone availability which is associated with enhanced GR activation. This does not affect gluconeogenesis and DNL, but could be linked to stimulated triglyceride synthesis and hypertriglyceridemia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Ovário Policístico
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Endocrine
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article