Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance.
Pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone stimulate the gonads by regulating germ cell proliferation and differentiation. FSH receptors (FSH-Rs) are localized to testicular Sertoli cells and ovarian granulosa cells and are coupled to activation of the adenylyl cyclase and other signaling pathways. Activation of FSH-Rs is considered essential for folliculogenesis in the female and spermatogenesis in the male. We have generated mice lacking FSH-R by homologous recombination. FSH-R-deficient males are fertile but display small testes and partial spermatogenic failure. Thus, although FSH signaling is not essential for initiating spermatogenesis, it appears to be required for adequate viability and motility of the sperms. FSH-R-deficient females display thin uteri and small ovaries and are sterile because of a block in folliculogenesis before antral follicle formation. Although the expression of marker genes is only moderately altered in FSH-R -/- mice, drastic sex-specific changes are observed in the levels of various hormones. The anterior lobe of the pituitary gland in females is enlarged and reveals a larger number of FSH- and thyroid-stimulating hormone (TSH)-positive cells. The phenotype of FSH-R -/- mice is reminiscent of human hypergonadotropic ovarian dysgenesis and infertility.
Dierich
A
A
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, 163, 67404 Illkirch, Strasbourg, France.
Sairam
M R
MR
Monaco
L
L
Fimia
G M
GM
Gansmuller
A
A
LeMeur
M
M
Sassone-Corsi
P
P
D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000378:metabolism*
D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone