Please use this identifier to cite or link to this item: https://doi.org/10.1210/en.2015-1733
Title: A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome
Authors: Lee, Bao Hui
Indran, Inthrani Raja 
Tan, Huey Min 
Li, Yu
Zhang, Zhiwei
Li, Jun
Yong, Eu-Leong 
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
HORMONE-BINDING GLOBULIN
NUCLEAR RECEPTOR NUR77
3-BETA-HYDROXYSTEROID DEHYDROGENASE
INSULIN SENSITIVITY
ANDROGEN PRODUCTION
THECA CELLS
STEROIDOGENIC ENZYMES
OBESE WOMEN
METFORMIN
TESTOSTERONE
Issue Date: 1-Jan-2016
Publisher: ENDOCRINE SOC
Citation: Lee, Bao Hui, Indran, Inthrani Raja, Tan, Huey Min, Li, Yu, Zhang, Zhiwei, Li, Jun, Yong, Eu-Leong (2016-01-01). A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome. ENDOCRINOLOGY 157 (1) : 382-394. ScholarBank@NUS Repository. https://doi.org/10.1210/en.2015-1733
Abstract: Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMPstimulated pathway. Specifically, bothDAand metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.
Source Title: ENDOCRINOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/206177
ISSN: 00137227
19457170
DOI: 10.1210/en.2015-1733
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