TY - JOUR
T1 - The molecular basis of impaired follicle-stimulating hormone action
T2 - Evidence from human mutations and mouse models
AU - Siegel, Eric T.
AU - Kim, Hyung Goo
AU - Nishimoto, Hiromi Koso
AU - Layman, Lawrence C.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Portions of this work were supported by the NICHD PHS-HD33004 to LCL.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - FSH receptor
KW - FSHB gene
KW - FSHB knockout mouse
KW - FSHB mutations
KW - FSHB transgenic mouse
KW - FSHR gene
KW - FSHR knockout mouse
KW - FSHR mutations
KW - Follicle-stimulating hormone (FSH)
KW - isolated FSH deficiency
KW - ovarian hyperstimulation syndrome
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U2 - 10.1177/1933719112461184
DO - 10.1177/1933719112461184
M3 - Review article
C2 - 23184658
AN - SCOPUS:84874452235
SN - 1933-7191
VL - 20
SP - 211
EP - 233
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 3
ER -