Background:
Propagating life to the next generation is a hormone-dependent process relying on the individual wish to generate own progeny and resulting in maintenance of species. Follicle-Stimulating Hormone (FSH) is a key reproductive hormone in vertebrates used as a drug in the treatment of human infertility and hypogonadism. The FSH-FSH receptor system began to be characterized in its essential functioning mechanism only in the last couple of decades, i.e. long after the clinical use of the hormone. One consequence thereof is that the most popular clinical use of FSH, i.e. stimulation of multiple follicular growth in assisted reproduction, is mostly empirical and not evidence-based.

It is textbook knowledge that FSH stimulates follicular growth and oogenesis in the female and spermatogenesis in the male via binding to its receptor, a member of the family of G protein-coupled receptors (GPCRs) activating the steroidogenic cAMP pathway. However, current basic and clinical research is revealing that the picture is not that simplistic. The role of FSH is not the same in the different species, the molecule itself exists as a complex pattern of isoforms due to glycosylation, the hormone activates multiple signal transduction pathways and interacts with other GPCRs. The picture is enriched by clinical data demonstrating that type of FSH used in therapy and the clinical response are quite heterogeneous. The discovery of spontaneous mutations and polymorphisms, in vivo studies with transgenic mice and in vitro studies reveal novel and unexpected phenotypes and mechanisms.

This is a short list of some of the research challenges we are now facing:
- Why is FSH absolutely necessary for fertility in some species and not in others?
- How does FSH interact with other hormone-receptor systems (e.g. -but not exclusively-Luteinizing Hormone and its receptor) in the cells where the FSHR is expressed? How do these interactions contribute to the apparent pleotropic and
sometimes even redundant interplay between the two gonadotropins?
- Did we collect the whole knowledge about FSH-mediated signaling and FSHR structure-functions?
- Is FSH helpful to expand the temporal fertility window in females?
- Can we effectively base novel therapeutic approaches to infertility on genetic variants of FSH and its receptor (pharmacogenetics)?
- Can we develop low molecular weight, selective FSH analogs stimulating/modulating specific effects?
- Is it possible to block some specific action/mechanism of FSH for contraceptive purposes?
- Does FSH have a role in cancer and other diseases?

Details for authors:
This Research Topic intends to collect together the most recent advancements in the field, covering both basic and clinical aspects. Evidence should be provided in support of therapeutic schemes based on mechanistic data and powerful clinical studies. Overall, the intent of this Research Topic is to fill the gap between demand (of infertility treatment) and offer (of drugs/therapeutic schemes) with solid science, with a special attention to the expanding spectrum of FSH actions. This project should provide a translational overview on FSH action in all models currently available.

We welcome contributions of any type (review articles, original papers, opinions) on the following Topics around FSH and the FSHR:

Role of glycosylation of FSH action
Small FSH analogs
Structure-function relationships of the FSHR
Transgenic models of FSH action
Role of FSH on spermatogenesis
Modulation of FSH activity by antibodies
Molecular mechanism of action of FSH
Biased signaling and allosteric modulators of the FSHR
FSHR transactivation and oligomerization
Intracellular FSH receptor trafficking
Extragonadal actions of FSH
Follitropin alfa, beta, delta and biosimilars: identity, similarities and differences
Effects of FSH on sperm DNA
Clinical use of FSH in male infertility
Pharmacogenetics of FSH action in the female
Pharmacogenetics of FSH action in the male
Role of FSH and FSHR in follicular growth and PCOS
FSHR polymorphism and PCOS
Individualization of FSH doses in assisted reproduction
FSH and cancer

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Frontiers in Endocrinology

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