PMID- 35433952
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 10
IP  - 6
DP  - 2022 Mar
TI  - RAF1 mediates the FSH signaling pathway as a downstream molecule to stimulate 
      estradiol synthesis and secretion in mouse ovarian granulosa cells.
PG  - 314
LID - 10.21037/atm-22-393 [doi]
LID - 314
AB  - BACKGROUND: The v-raf-leukemia viral oncogene 1 (RAF1) plays an essential 
      physiological role in reproduction and development through the mediation of 
      steroid hormone synthesis. Follicle-stimulating hormone (FSH) signaling pathway 
      was not involved in the majority of RAF1 studies, whether RAF1 takes part in the 
      signaling events of gonadotropic hormones such as FSH in ovarian tissue is 
      unknown. METHODS: The process is blocked by treating granulosa cells (GCs) with 
      the RAF1 inhibitor, RAF709. Inhibition of RAF1 activity by RAF709 decreased 
      extracellular regulated protein kinases (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. 
      RESULTS: We found that RAF1, acting as a downstream molecule, mediates FSH 
      signalling to stimulate estradiol (E2) synthesis and secretion in mouse ovarian 
      GCs. Gene expression of RAF1 was induced by FSH and the secretion of E2 increased 
      into the bloodstream of mice and into the supernatant of primary GCs. Our in 
      vitro and in vivo studies clearly illustrate RAF1 plays an important medium 
      adjusting role in the FSH signaling pathway, and RAF1 acting as a downstream 
      molecule to trigger ERK phosphorylation to stimulate GC E2 synthesis and 
      secretion. CONCLUSIONS: RAF1 plays a pivotal mediating role in the FSH signaling 
      pathway by inducing the phosphorylation of ERK and promoting E2 synthesis.
CI  - 2022 Annals of Translational Medicine. All rights reserved.
FAU - Luo, Xuan
AU  - Luo X
AD  - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China 
      Agricultural University, Beijing, China.
FAU - Liu, Hui
AU  - Liu H
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
FAU - Guo, Hongzhou
AU  - Guo H
AD  - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China 
      Agricultural University, Beijing, China.
FAU - Sun, Longjie
AU  - Sun L
AD  - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China 
      Agricultural University, Beijing, China.
FAU - Gou, Kemian
AU  - Gou K
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
FAU - Cui, Sheng
AU  - Cui S
AD  - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China 
      Agricultural University, Beijing, China.
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9011243
OTO - NOTNLM
OT  - V-raf-leukemia viral oncogene 1 (RAF1)
OT  - estradiol secretion
OT  - mouse ovarian granulosa cells
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-393/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2022/04/19 06:00
MHDA- 2022/04/19 06:01
PMCR- 2022/03/01
CRDT- 2022/04/18 06:40
PHST- 2021/12/23 00:00 [received]
PHST- 2022/03/16 00:00 [accepted]
PHST- 2022/04/18 06:40 [entrez]
PHST- 2022/04/19 06:00 [pubmed]
PHST- 2022/04/19 06:01 [medline]
PHST- 2022/03/01 00:00 [pmc-release]
AID - atm-10-06-314 [pii]
AID - 10.21037/atm-22-393 [doi]
PST - ppublish
SO  - Ann Transl Med. 2022 Mar;10(6):314. doi: 10.21037/atm-22-393.