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RAF1 mediates the FSH signaling pathway as a downstream molecule to stimulate estradiol synthesis and secretion in mouse ovarian granulosa cells

Xuan Luo, Hui Liu, Hongzhou Guo, Longjie Sun, Kemian Gou, Sheng Cui

Abstract

The v-raf-leukemia viral oncogene 1 (RAF1) plays an essential physiological role in reproduction and development through the mediation of steroid hormone synthesis. However, whether RAF1 takes part in the signaling events of gonadotropic hormones such as follicle-stimulating hormone (FSH) in ovarian tissue is unknown. We found that RAF1, acting as a downstream molecule mediates FSH signaling to stimulate estradiol (E2) synthesis and secretion in mouse ovarian granulosa cells (GCs). Gene expression of RAF1 is induced by FSH and the production of E2 is increased in mouse serum and primary supernatant of GCs. The process is blocked by treating GCs with the RAF1 inhibitor, RAF709. Inhibition of RAF1 activity by RAF709 decreased ERK phosphorylation and suppressed the expression of the cytochrome P450 subfamily 19 member 1 (CYP19A1), which is a major rate-limiting enzyme that participates in the last step of E2 biosynthesis. Our results suggest that RAF1 plays a pivotal mediating role in the FSH signaling pathway by inducing the phosphorylation of ERK and promoting E2 synthesis.

RD20302  Accepted 03 February 2021

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