The FSH/FSHR axis in reproductive biology and oncogenesis: mechanisms and emerging targeted therapies†.

Follicle-stimulating hormone (FSH) and its receptor (FSHR) constitute one of the core signaling axes that regulate the reproductive process of mammals. Studies have shown that the glycosylation pattern of FSH and the polymorphism of receptor genes can affect the ligand-receptor binding efficiency and downstream signal intensity, and are related to the susceptibility and phenotype of diseases such as polycystic ovary syndrome and primary ovarian insufficiency. FSH/FSHR not only regulates normal reproductive function by activating multiple pathways such as cyclic adenosine monophosphate/protein kinase A, PI3K/Akt, β-arrestin, and MEK/ERK, but also promotes the progression of malignant tumors such as ovarian cancer and prostate cancer through mechanisms like activation of cancer stem cells, metabolic reprogramming, and angiogenesis. Therefore, targeting the FSH/FSHR axis has become a highly promising therapeutic strategy. This review summarizes the latest research advances of FSH/FSHR axis in reproductive system diseases and tumors, especially the therapeutic value of FSH/FSHR signaling axis.