Stem Cell Biology Department, ICMR- National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Maharashtra, 400012, Mumbai, India.
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
J Ovarian Res. 2021 Oct 30;14(1):144. doi: 10.1186/s13048-021-00880-3.
FSH was first identified in 1930 and is central to mammalian reproduction. It is indeed intriguing that despite being researched upon for about 90 years, there is still so much more to learn about FSH-FSHR biology. The purpose of this review is to provide an overview of current understanding of FSH-FSHR biology, to review published data on biological and clinical relevance of reported mutations, polymorphisms and alternately spliced isoforms of FSHR. Tissue-resident stem/progenitor cells in multiple adult tissues including ovaries, testes and uterus express FSHR and this observation results in a paradigm shift in the field. The results suggest a direct action of FSH on the stem cells in addition to their well-studied action on Granulosa and Sertoli cells in the ovaries and testes respectively. Present review further addresses various concerns raised in recent times by the scientific community regarding extragonadal expression of FSHR, especially in cancers affecting multiple organs. Similar population of primitive and pluripotent tissue-resident stem cells expressing FSHR exist in multiple adult tissues including bone marrow and reproductive tissues and help maintain homeostasis throughout life. Any dysfunction of these stem cells results in various pathologies and they also most likely get transformed into cancer stem cells and initiate cancer. This explains why multiple solid as well as liquid tumors express OCT-4 and FSHR. More research efforts need to be focused on alternately spliced FSHR isoforms.
促卵泡激素（FSH）于 1930 年首次被发现，是哺乳动物生殖的核心。尽管已经研究了大约 90 年，但对于 FSH-FSHR 生物学仍有很多需要了解，这确实令人着迷。本文的目的是提供对 FSH-FSHR 生物学的当前理解的概述，回顾已发表的关于 FSHR 的报道的突变、多态性和交替剪接异构体的生物学和临床相关性的数据。多种成年组织中的组织驻留干细胞/祖细胞，包括卵巢、睾丸和子宫，表达 FSHR，这一观察结果导致该领域发生范式转变。结果表明，FSH 除了对卵巢和睾丸中的颗粒细胞和支持细胞的研究作用外，还直接作用于干细胞。本综述进一步讨论了科学界最近就 FSHR 的性腺外表达提出的各种关注，特别是在影响多个器官的癌症中。在包括骨髓和生殖组织在内的多种成年组织中，存在着表达 FSHR 的类似原始和多能组织驻留干细胞群体，有助于维持整个生命周期的内稳态。这些干细胞的任何功能障碍都会导致各种病理，它们也很可能转化为癌症干细胞并引发癌症。这解释了为什么多种实体瘤和液体瘤都表达 OCT-4 和 FSHR。需要更多的研究努力集中在交替剪接的 FSHR 异构体上。
