Fshr, the follicle-stimulating hormone receptor, belongs to the G protein-coupled receptors (GPCRs) family. It is crucial for human reproduction as it binds follicle-stimulating hormone (FSH), inducing spermatogenesis in men and estrogen production in women when expressed on granulosa and Sertoli cells [1]. FSHR activation also involves Gαs coupling and other Gα subunits in some cases, along with the recruitment of G protein-coupled receptor kinases and β-arrestins for desensitization, trafficking, and intracellular signaling [4].

The expression of Fshr has been detected not only in gonadal tissues but also in extragonadal normal and tumorous tissues [2]. However, there are concerns about the validity of some findings regarding extragonadal expression, such as issues with antibody-based protein detection and discrepancies between gene and protein levels [2]. In addition, Fshr polymorphisms, like rs6165 and rs6166, may modulate susceptibility to polycystic ovary syndrome (PCOS) in a population-specific manner [3,6]. Also, Fshr antagonists can potentially trigger a PCOS-like state [5].

In conclusion, Fshr is essential for reproductive functions by mediating the effects of FSH. Research on Fshr, including through gene polymorphisms and antagonist studies, has implications for understanding and treating reproductive-related diseases like PCOS. The complex expression patterns of Fshr, especially in extragonadal tissues, also highlight the need for more accurate validation methods in future studies.