Mutations of follicle-stimulating hormone and its receptor: effects on gonadal function

Abstract

The physiological functions of the two gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are quite well known in both males and females. Nevertheless, the recent unraveling of structures of the gonadotropin and gonadotropin receptor genes has provided us with tools to obtain completely new information on the functions of these hormones at the molecular level. Several gain-and loss-of-function mutations of these genes have been discovered in humans, and the first knock-out experiments with these genes in the mouse have been recently published. The purpose of the present review is to describe the current state of knowledge on human mutations of FSH and its receptor, as well as on relevant animal models.

IgG, IgA and IgM Antibodies against FSH: Serological Markers of Pathogenic Autoimmunity or of Normal Immunoregulation?

“…Some of AOA‐positive IVF patients also presented autoantibodies against FSH, as shown previously by Gobert et al 8 The FSH and its signaling system play a central role in the normal reproductive function, regulating follicular maturation and ovulation 9 . Mutations in human FSH and its receptor are associated with altered ovarian responses to the hormone, resulting in various degrees of reduced reproductive function 10–14 . Conversely, immunization against FSH has been discussed as promising approach to contraception in males, 15,16 supporting the concept that autoimmune reactions towards this hormone could be involved in gonadal failure and infertility.…”

Association of FSH receptor promoter’s polymorphisms with IVF-failure in Iranian women

“…It has been shown that FSHR knockout mice were infertile and their phenotype was similar to the one observed in infertile women with an inactivating mutation in FSHR. 8 In addition, the polymorphisms in the promoter and coding region of FSHR gene have been studied in association to ovarian responses in women (g._29G>A, p.Thr307Ala and p.Asn680Ser). 8 Although some studies suggested the coding region polymorphisms as a potential predictor marker for ovarian response, others demonstrated no significant association.…”

“…8 In addition, the polymorphisms in the promoter and coding region of FSHR gene have been studied in association to ovarian responses in women (g._29G>A, p.Thr307Ala and p.Asn680Ser). 8 Although some studies suggested the coding region polymorphisms as a potential predictor marker for ovarian response, others demonstrated no significant association. [9][10][11][12][13] FSHR core promoter region shows five single nucleotide polymorphisms, at positions -29, -37, -114, -123 and -138, that have been reported to be associated with higher level of FSH and various ovarian responses to FSH in IVF at different populations.…”

Effects of long-term treatment with human pure follicle-stimulating hormone on semen parameters and sperm-cell ultrastructure in idiopathic oligoteratoasthenozoospermia

“…The well‐known discrepancies between the biological activity of FSH and its immunoreactivity suggest that a qualitative hormone defect could be somehow involved in these clinical alterations (Schill, 1995). Furthermore, it has been shown that serum FSH is a mixture of microheterogeneous isoforms which vary in different physiological and pathological conditions (Huhtaniemi & Aittomaki, 1998). Finally, several gain‐ and loss‐of‐function mutations of FSH and FSH‐receptor genes (i.e.…”