The Molecular Basis of Impaired Follicle-Stimulating Hormone Action: Evidence From Human Mutations and Mouse Models

The pituitary gonadotropin follicle-stimulating hormone (FSH) interacts with its membrane-bound receptor to produce biologic effects. Traditional functions of FSH include follicular development and estradiol production in females, and the regulation of Sertoli cell action and spermatogenesis in male...

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Bibliographic Details
Published in:Reproductive Sciences 2013-03, Vol.20 (3), p.211-233
Main Authors: Siegel, Eric T., Kim, Hyung-Goo, Nishimoto, Hiromi Koso, Layman, Lawrence C.
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Embryology
Female
Follicle Stimulating Hormone - blood
Follicle Stimulating Hormone - genetics
Gonadal Disorders - blood
Gonadal Disorders - diagnosis
Gonadal Disorders - genetics
Humans
Male
Medicine & Public Health
Mice
Mutation - genetics
Obstetrics/Perinatology/Midwifery
Receptors, FSH - blood
Receptors, FSH - genetics
Reproductive Medicine
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Summary:The pituitary gonadotropin follicle-stimulating hormone (FSH) interacts with its membrane-bound receptor to produce biologic effects. Traditional functions of FSH include follicular development and estradiol production in females, and the regulation of Sertoli cell action and spermatogenesis in males. Knockout mice for both the ligand (Fshb) and the receptor (Fshr) serve as models for FSH deficiency, while Fshb and Fshr transgenic mice manifest FSH excess. In addition, inactivating mutations of both human orthologs (FSHB and FSHR) have been characterized in a small number of patients, with phenotypic effects of the ligand disruption being more profound than those of its receptor. Activating human FSHR mutants have also been described in both sexes, leading to a phenotype of normal testis function (male) or spontaneous ovarian hyperstimulation syndrome (females). As determined from human and mouse models, FSH is essential for normal puberty and fertility in females, particularly for ovarian follicular development beyond the antral stage. In males, FSH is necessary for normal spermatogenesis, but there are differences in human and mouse models. The FSHB mutations in humans result in azoospermia; while FSHR mutations in humans and knockouts of both the ligand and the receptor in mice affect testicular function but do not result in absolute infertility. Available evidence also indicates that FSH may also be necessary for normal androgen synthesis in males and females.
ISSN:1933-7191
1933-7205
DOI:10.1177/1933719112461184