Fshr, the follicle-stimulating hormone receptor, belongs to the G protein-coupled receptors (GPCRs) family. It plays a key role in human reproduction. FSH binds to Fshr expressed on the surface of target cells (granulosa and Sertoli cells), inducing spermatogenesis in men and estrogen production in women [1].

The crystal structure and experimental evidence have shown that Fshr can self-associate and form heterodimers with the luteinizing hormone/chorionic gonadotropin receptor-LHCGR. There is also evidence of trans-activation and biased signaling between GPCRs [1]. Fshr has been detected in extragonadal normal and tumorous tissues, suggesting potential roles in angiogenesis, myometrial contractility, skeletal integrity, and adipose tissue accumulation, though the validity of some of these findings has been questioned due to issues in research methods [2]. Polymorphisms in Fshr, such as rs6165 and rs6166, may modulate susceptibility to polycystic ovary syndrome (PCOS) in a population-specific manner [4,6]. Fshr antagonists may trigger a PCOS-like state [5]. Tissue-resident stem/progenitor cells in multiple adult tissues express Fshr and respond to FSH via an alternatively spliced FSHR-3, which may explain Fshr expression in cancer cells [3,7]. FSHR SNPs rs6165, rs6166, and rs1394205 might affect male spermatogenic dysfunction [8].

In conclusion, Fshr is crucial for reproduction and may be involved in various extragonadal functions and diseases like PCOS and male infertility. Studies on Fshr, including those related to its polymorphisms, oligomerization, and expression in different cell types, help to understand its complex biological functions and its implications in disease development, providing potential targets for therapeutic intervention.

References:

1. Szymańska, Kamila, Kałafut, Joanna, Przybyszewska, Alicja, Kiełbus, Michał, Rivero-Müller, Adolfo. 2018. FSHR Trans-Activation and Oligomerization. In Frontiers in endocrinology, 9, 760. doi:10.3389/fendo.2018.00760. https://pubmed.ncbi.nlm.nih.gov/30619090/

2. Chrusciel, Marcin, Ponikwicka-Tyszko, Donata, Wolczynski, Slawomir, Huhtaniemi, Ilpo, Rahman, Nafis A. 2019. Extragonadal FSHR Expression and Function-Is It Real? In Frontiers in endocrinology, 10, 32. doi:10.3389/fendo.2019.00032. https://pubmed.ncbi.nlm.nih.gov/30778333/

3. Bhartiya, Deepa, Patel, Hiren. 2021. An overview of FSH-FSHR biology and explaining the existing conundrums. In Journal of ovarian research, 14, 144. doi:10.1186/s13048-021-00880-3. https://pubmed.ncbi.nlm.nih.gov/34717708/

4. Kaur, Mandeep, Singh, Sukhjashanpreet, Kaur, Anupam. 2023. Polymorphisms in FSHR modulating susceptibility to polycystic ovary syndrome: an updated meta-analysis. In Journal of ovarian research, 16, 183. doi:10.1186/s13048-023-01238-7. https://pubmed.ncbi.nlm.nih.gov/37653412/

5. Waghu, Faiza Hanif, Desai, Karishma, Srinivasan, Sumana, Venkatesh, Kareenhalli V, Idicula-Thomas, Susan. 2021. FSHR antagonists can trigger a PCOS-like state. In Systems biology in reproductive medicine, 68, 129-137. doi:10.1080/19396368.2021.2010837. https://pubmed.ncbi.nlm.nih.gov/34967272/

6. Laven, Joop S E. 2019. Follicle Stimulating Hormone Receptor (FSHR) Polymorphisms and Polycystic Ovary Syndrome (PCOS). In Frontiers in endocrinology, 10, 23. doi:10.3389/fendo.2019.00023. https://pubmed.ncbi.nlm.nih.gov/30809190/

7. Bhartiya, Deepa, Patel, Hiren, Kaushik, Ankita, Singh, Pushpa, Sharma, Diksha. 2021. Endogenous, tissue-resident stem/progenitor cells in gonads and bone marrow express FSHR and respond to FSH via FSHR-3. In Journal of ovarian research, 14, 145. doi:10.1186/s13048-021-00883-0. https://pubmed.ncbi.nlm.nih.gov/34717703/

8. Wu, Qiu-yue, Shui, Ying-chun, Xia, Xin-yi, Huang, Yu-feng. . [FSH and FSHR gene polymorphisms and male infertility: An update]. In Zhonghua nan ke xue = National journal of andrology, 21, 1031-4. doi:. https://pubmed.ncbi.nlm.nih.gov/26738333/