Regulation of the Activin-Inhibin-Follistatin System by Bone Morphogenetic Proteins in the Zebrafish Ovary
- Authors
- Li, C.W., and Ge, W.
- ID
- ZDB-PUB-130712-24
- Date
- 2013
- Source
- Biology of reproduction 89(3): 55 (Journal)
- Registered Authors
- Ge, Wei
- Keywords
- activin, inhibin, ovary, zebrafish, bone morphogenetic protein
- MeSH Terms
-
- Activins/genetics*
- Activins/metabolism
- Animals
- Bone Morphogenetic Proteins/physiology*
- CHO Cells
- Cells, Cultured
- Cricetinae
- Cricetulus
- Female
- Follistatin/genetics*
- Follistatin/metabolism
- Gene Expression Regulation*
- Inhibins/genetics*
- Inhibins/metabolism
- Ovarian Follicle/growth & development*
- Ovarian Follicle/metabolism
- Signal Transduction/physiology
- Zebrafish/genetics
- Zebrafish/physiology*
- PubMed
- 23843234 Full text @ Biol. Reprod.
In the zebrafish, the dynamic expression of the activin-inhibin-follistatin system during folliculogenesis and its exclusive localization (except follistatin) in the follicle cells suggest that the system plays important roles in follicle development and its expression is subject to tight controls, probably by external factors including those derived from the oocyte. We have previously identified zebrafish bone morphogenetic proteins (BMPs) as oocyte factors that may act on the follicle cells; however, the targets of BMPs in the follicle cells remain unknown. Considering their spatiotemporal expression in the follicle, we hypothesized that members of the activin-inhibin-follistatin system in the follicle cells could be potential target genes of BMPs. In the present study, we developed a novel co-culture system to co-incubate zfBMP2b/4-producing CHO cells with zebrafish follicle cells. During incubation, the zfBMPs secreted from the CHO cells would act directly on the follicle cells in a paracrine manner. Our results showed that all activin beta subunits (inhbaa, inhbab and inhbb) were down-regulated by both zfBMP2b and zfBMP4, while follistatin (fst, activin-binding protein) and inhibin alpha (inha, activin antagonist) were significantly up-regulated. The specificity of BMP actions was confirmed by siRNA knockdown of zfBMP4 expression in the CHO cells. The robust response of inha to zfBMPs, together with our previous observation that inha expression surged at the full-grown stage prior to oocyte maturation, has led us to hypothesize that the full-grown oocyte may signal the upper levels of the hypothalamic-pituitary-gonadal axis for its readiness to mature by releasing BMPs, which in turn stimulate inhibin production. As an ovarian hormone and activin antagonist, inhibin may suppress the action of activin in the pituitary to reduce FSH but increase LH biosynthesis. Meanwhile, by increasing local follistatin level and reducing activin production, BMPs could help prevent precocious maturation before preovulatory LH surge.