Importance of LH and LHCGR expression in Women and Men

This Research Topic will explore the pivotal role of luteinising hormone (LH) and its receptor (LHCGR) in human reproductive physiology and infertility treatments. It will highlight both the established and emerging functions of LH/LHCGR in ovarian and testicular processes, as well as their therapeutic implications in assisted reproduction, while identifying key areas requiring further research.

In women, LHCGR is expressed across ovarian cell types and undergoes dynamic regulation throughout the menstrual cycle. Its expression is modulated by FSH and oestrogens before ovulation, transiently downregulated by the LH surge, and later reactivated by hCG to support luteal function. However, whether LHCGR exists in distinct functional forms across ovarian cells remains unclear. In assisted reproductive technologies (ART), exogenous LH and hCG are routinely used, yet the precise thresholds of LH activity and the consequences for LHCGR regulation and follicular development are still poorly defined. This is particularly relevant for conditions such as polycystic ovary syndrome (PCOS), where altered LH levels and LHCGR gene polymorphisms may disrupt normal ovarian function.

In men, LHCGR expressed on Leydig cells is essential for testosterone production, spermatogenesis, and fetal masculinization. Clinical use of hCG, with or without FSH, is crucial for managing hypogonadotropic hypogonadism, delayed puberty, cryptorchidism, and male infertility. However, more research is needed applying animal models relevant for the human to understand mechanisms of LHCGR upregulation and the role of LH activity in male infertility to improve treatment strategies.

Overall, while LH is fundamental for steroidogenesis and reproductive function in both sexes, the mechanisms of LHCGR regulation—particularly its up- and downregulation in response to different gonadotropins—remain incompletely understood. Clarifying these interactions is essential for refining therapeutic approaches and improving reproductive outcomes in women and men.

This Research Topic will provide a comprehensive overview of the roles of LH and the LHCGR in normal human physiology and in treatment of infertility of women and men. Therapeutic approaches for treatment of infertility are often based on beliefs or trial & error, mainly due to the lack of conclusive research data. Therefore, this overview will also summarise the gaps in our understanding of the role of LH and LHCGR in reproductive physiology and will advise on future research to expand and improve treatment options for infertile women and men.

To gather further insights into the complexities of LH and LHCGR in reproductive health, we welcome articles addressing, but not limited to, the following themes:

o The regulatory mechanisms of LHCGR expression in ovarian and testicular cells.

o The interplay of LH and LHCGR in conditions like PCOS and their therapeutic implications.

o The role of LHCGR polymorphisms in fertility disorders.

o Critical insights into ART and the LH activity thresholds and ceilings of different gonadotropins .

o Exploring LHCGR upregulation in male reproductive treatments.