کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5505122 | 1400261 | 2017 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of testicular steroidogenesis by Foxa3 via transcriptional modulation of ERα signaling in type 2 diabetes mellitus (T2DM)
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice. Functionally, upon hCG stimulation, Foxa3 recruits to the Esr1 promoter and suppresses the transactivation of Esr1 gene. Disruption of this recruitment by T2DM-elicited hyperinsulinemia led to abnormal activation of ERα pathway, inhibited steroidogenic enzyme genes expression, and thus caused inadequate T production. Therapeutically, insulin-impaired and Foxa3 ablation-compromised steroidogenesis were effectively rescued by a pharmacological inhibitor of the ERα pathway. These findings reveal an obligatory coregulatory role of Foxa3 in the regulation of ERα expression and of the Foxa3/ERα cascade, at least in part, in the pathogenesis of androgen deficiency caused by T2DM.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 490, Issue 3, 26 August 2017, Pages 786-793
Journal: Biochemical and Biophysical Research Communications - Volume 490, Issue 3, 26 August 2017, Pages 786-793
نویسندگان
Yong Zhao, Hong-xin Li, Ke Wang, Bin-yuan Yan, Wei Li,