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

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Abstract

The pituitary gonadotropin follicle-stimulating hormone (FSH) interacts with its membrane-bound receptor to produce biologic effects. Traditional functions of FSH include follicular development estradiol production in females the regulation of Sertoli cell action spermatogenesis in males. Knockout mice for both the ligand (Fshb) the receptor (Fshr) serve as models for FSH deficiency while Fshb Fshr transgenic mice manifest FSH excess. In addition inactivating mutations of both human orthologs (FSHB 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 mouse models FSH is essential for normal puberty 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 mouse models. The FSHB mutations in humans result in azoospermia; while FSHR mutations in humans knockouts of both the ligand 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 females.

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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Section of Reproductive Endocrinology, Infertility, & Genetics, Medical College of Georgia, Georgia Health Sciences University, 1120 15th Street, Augusta, GA, 30912, USA

    Eric T. Siegel MD, Hyung-Goo Kim PhD, Hiromi Koso Nishimoto MD & Lawrence C. Layman MD

  2. The Institute of Molecular Medicine Genetics, Georgia Health Sciences University, Augusta, GA, USA

    Hyung-Goo Kim PhD & Lawrence C. Layman MD

  3. Neuroscience Program, Georgia Health Sciences University, Augusta, GA, USA

    Lawrence C. Layman MD

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  1. Eric T. Siegel MD
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  2. Hyung-Goo Kim PhD
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  3. Hiromi Koso Nishimoto MD
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  4. Lawrence C. Layman MD
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Correspondence to Lawrence C. Layman MD.

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Siegel, E.T., Kim, HG., Nishimoto, H.K. et al. The Molecular Basis of Impaired Follicle-Stimulating Hormone Action: Evidence From Human Mutations and Mouse Models. Reprod. Sci. 20, 211–233 (2013). https://doi.org/10.1177/1933719112461184

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