Glucocorticoid prereceptor metabolism in the liver of 5α-dihidrotestosterone-treated rats as animal model of polycystic ovary syndrome
2017
Аутори:
Jelača, SanjaBrkljačić, Jelena
Veličković, Nataša
Teofilović, Ana
Đorđević, Ana
Radovanović, Marina
Macut, Đuro
Božić-Antić, Ivana
Matić, Gordana
Vojnović-Milutinović, Danijela
Остала ауторства
Brajušković, GoranĐorđević, Ana
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2017 University of Belgrade, Faculty of Biology
Метаподаци
Приказ свих података о документуАпстракт:
Introduction: Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, visceral obesity and insulin resistance. PCOS is also associated with enhanced cortisol metabolite excretion, as well as with altered peripheral glucocorticoid metabolism, which is inevitably linked to insulin resistance characteristic for women with PCOS. The main enzymes involved in glucocorticoid prereceptor metabolism are 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) that regenerates corticosterone from its inactive precursor, and 5α and 5β reductases (5αR and 5βR) that inactivate corticosterone. In this study, female rats treated with nonaromatizable 5α-dihydrotestosterone (DHT) were used as an animal model of PCOS and the aim was to examine whether this treatment affects hepatic glucocorticoid prereceptor metabolism.
Methods: We analyzed the effects of prolonged treatment of prepubertal rats with DHT on body and liver masses, and plasma and liver corticosterone levels. The expression of hepatic 11βHSD1, hexose-6-phosphate dehydrogenase (H6PDH), 5αR, 5βR and glucocorticoid receptor (GR) were analyzed by real-time PCR and Western blot methods.
Results: DHT treatment induced an increase in body and liver masses, an elevation of hepatic 11βHSD1 expression and a reduction of 5αR mRNA level, leading to tissue corticosterone rise and GR nuclear accumulation. In addition, H6PDH and 5βR mRNA levels remained unchanged.
Conclusion: DHT treatment affected hepatic glucocorticoid prereceptor metabolism through enhanced corticosterone availability and its decreased inactivation, which led to enhanced GR activation. Further studies should reveal possible link between enhanced hepatic glucocorticoid signaling and metabolic disturbances observed in PCOS.
Финансирање / пројекти:
- Улога стероидних хормона у неуроендокриној адаптацији на стрес и патофизиологији метаболичког синдрома - молекуларни механизми и клиничке импликације (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41009)
У:
- Brajušković G, Đorđević A, editors. CoMBoS. Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. Belgrade: University of Belgrade, Faculty of Biology; 2017. p. 42.