Deregulation of WNT2/FZD3/β-catenin pathway compromises the estrogen synthesis in cumulus cells from patients with polycystic ovary syndrome
| Autor: | Bi-liang Chen, Chang-you Yan, Chao-juan Zhu, Gu-yuan Qiao, Bing-wei Dong |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Cell signaling Frizzled medicine.drug_class Granulosa cell Biophysics Down-Regulation Biology Biochemistry Wnt2 Protein 03 medical and health sciences WNT2 Internal medicine medicine Humans Wnt Signaling Pathway Molecular Biology Cells Cultured beta Catenin Estrogen receptor beta Cumulus Cells Wnt signaling pathway Estrogens Cell Biology Polycystic ovary Frizzled Receptors 030104 developmental biology Endocrinology Estrogen Cancer research Female Polycystic Ovary Syndrome |
| Zdroj: | Biochemical and Biophysical Research Communications. 493:847-854 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2017.07.057 |
| Popis: | Mechanistic insight into estrogen deficiency by polycystic ovary syndrome (PCOS) remains a longstanding challenge in reproductive medicine. Recent advance suggest that Wingless-type MMTV integration site family members (WNTs), in concert with its Frizzled (FZD) receptors, regulate normal folliculogenesis, luteogenesis and ovarian steroidogenesis. However, no studies have so far investigated any causality between WNT-FZDs interactions and disrupted estrogen synthesis under certain pathological conditions. Here, we show that (i) FZD3 expression was significantly up-regulated in the cumulus cells (CCs) from PCOS patients. This up-regulation, along with the activation of WNT2/β-Catenin pathway, was tightly associated with insulin resistance and estrogen deficiency, two hallmarks of PCOS. (ii) Overexpression of exogenous FZD3 in human granulosa cell COV434 impaired long-term FSH incubation-induced CYP19A1 transactivation and the recruitment of β-Catenin onto CYP19A1 promoter, and subsequently compromised FSH-stimulated estrogen production. (iii) Conversely, inhibition of FZD3 expression exhibited a therapeutic effect on estrogen synthesis in PCOS CCs. Thus, excessive FZD3 expression in CCs may act as a brake on steroidogenic activation that is normally overcome by FSH stimulation. Future endeavor in this field should help to elucidate the complicated crosstalk between energy metabolism and endocrine cells through WNT/FZD signaling molecules. |
| Databáze: | OpenAIRE |
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