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- Title
Leptin Receptor Mediates Bmal1 Regulation of Estrogen Synthesis in Granulosa Cells.
- Authors
Chu, Guiyan; Ma, Guangjun; Sun, Jingchun; Zhu, Youbo; Xiang, Aoqi; Yang, Gongshe; Sun, Shiduo
- Abstract
Chronobiology affects female fertility in mammals. Lepr is required for leptin regulation of female reproduction. The presence of E-box elements in the Lepr promoter that are recognized and bound by clock genes to initiate gene transcription suggested that circadian systems might regulate fertility through Lepr . However, it is unclear whether Bmal1, a key oscillator controlling other clock genes, is involved in leptin regulation in hormone synthesis through Lepr. In this study, serum estradiol (E 2 ) concentration and the expressions of Bmal1 , Lepr , Cyp19a1 , and Cyp11a1 genes were found to display well-synchronized circadian rhythms. Knockdown of Bmal1 significantly reduced expression levels of Lepr , Fshr , and Cyp19a1 genes; protein production of Bmal1, Lep r , and Cyp19a1; and the E 2 concentration in granulosa cells. Knockdown of Lepr reduced the expression levels of Cyp19a1 and Cyp11a1 genes and Cyp19a1 protein, and also reduced E 2 concentration. Addition of leptin affected the expression of Cyp19a1 , Cyp11a1 , and Fshr genes. Bmal1 deficiency counteracted leptin-stimulated upregulation of the genes encoding E 2 synthesis in granulosa cells. These results demonstrated that Bmal1 participates in the process by which leptin acts on Lepr to regulate E 2 synthesis.
- Publication
Animals : an open access journal from MDPI, 2019, Vol 9, Issue 11
- ISSN
2076-2615
- Publication type
Journal Article
- DOI
10.3390/ani9110899