ZFIN ID: ZDB-PUB-140101-30
Differential Regulation of Kit Ligand A Expression in the Ovary by IGF-I via Different Pathways
Yao, K., Lau, S.W., and Ge, W.
Date: 2014
Source: Molecular endocrinology (Baltimore, Md.)   28(1): 138-150 (Journal)
Registered Authors: Ge, Wei
Keywords: none
MeSH Terms:
  • Animals
  • Cells, Cultured
  • Epidermal Growth Factor/physiology
  • Female
  • Gene Expression Regulation*
  • Insulin-Like Growth Factor I/physiology*
  • MAP Kinase Signaling System
  • Oogenesis
  • Ovarian Follicle/metabolism*
  • Ovary/cytology
  • Ovary/metabolism
  • Phosphatidylinositol 3-Kinases/metabolism
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-akt/metabolism
  • Receptor, IGF Type 1/metabolism
  • Stem Cell Factor/genetics*
  • Stem Cell Factor/metabolism
  • Transcription, Genetic
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 24243489 Full text @ Mol. Endocrinol.

Kit ligand (KITL) plays indispensable roles both in primordial follicle activation and in the maintenance of meiotic arrest of the oocyte. The regulation of KITL expression in the ovary, however, remains largely unknown. In the zebrafish, there are 2 paralogues of KITL, kitlga and kitlgb, and 2 Kit receptors, kita and kitb. Consistent with the situation in mammals, kitlga is only expressed in the ovarian follicle cells, and its cognate receptor kita is expressed in the oocyte. In the present study, we demonstrated that the expression of kitlga was promoted by IGF-I through its receptor IGF-IR. The stimulation involved transcription but not translation, suggesting that the kitlga gene is likely a direct downstream target of IGF-I signaling. Further experiments showed that the stimulatory effect of IGF-I was mediated by phosphatidyl inositol 3-kinase (PI3K)-Akt pathway. IGF-I also activated MEK-ERK pathway; however, this pathway suppressed kitlga expression. The regulation of kitlga expression by IGF-I appeared to depend on the stage of follicle development with a greater induction at early stage than late stage. This may be related to changes in IGF-I signaling pathways and/or local paracrine environment. In support of this were the differential expression of IGF-I receptors (igf1ra and igf1rb) and responsiveness of IGF-I signaling pathways, especially the PI3K-Akt pathway. Furthermore, the IGF-I-induced kitlga expression was inhibited by epidermal growth factor, an oocyte-derived paracrine factor in the zebrafish follicle. This study provides evidence for a controlling mechanism underlying the regulation of KITL expression in the ovary.