Conclusions
In addition to the central regulation, local ovarian overexpression of the NKB-NK3R system participated in the adverse reproductive endocrine phenotypes, supporting the therapeutic implications of NK3Ra for PCOS.
Results
The PCOS-like stimulations induced the NKB-NK3R system and MAPK-ERK pathway overexpression in KGN cells, in an approximate dose and time-dependent manner. The NKB-NK3R system overactivated the MAPK-ERK pathway to increase NNT overexpression, disturb NADH/NADPH pools, aggravate the oxidation state, and decrease ATP production. With overexpression of the NKB-NK3R system in the local ovarian tissue, ovulatory dysfunction, progesterone deficiency, and pro-inflammatory states were apparent in PCOS-like mice. Antagonizing the receptor, NK3R, reversed the adverse reproductive endocrine phenotypes via improving mitochondrial dysfunction. Conclusions: In addition to the central regulation, local ovarian overexpression of the NKB-NK3R system participated in the adverse reproductive endocrine phenotypes, supporting the therapeutic implications of NK3Ra for PCOS.