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 luteini zing hormone stimulate the gonads by regulating germ cell proliferatio n and differentiation. FSH receptors (FSH-Rs) are localized to testicu lar Sertoli cells and ovarian granulosa cells and are coupled to activ ation 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 dis play small testes and partial spermatogenic failure. Thus, although FS H signaling is not essential for initiating spermatogenesis, it appear s to be required for adequate viability and motility of the sperms. FS H-R-deficient females display thin uteri and small ovaries and are ste rile because of a block in folliculogenesis before antral follicle for mation. Although the expression of marker genes is only moderately alt ered in FSH-R -/- mice, drastic sex-specific changes are observed in t he revels of various hormones. The anterior lobe of the pituitary glan d in females is enlarged and reveals a larger number of FSH- and thyro id-stimulating hormone (TSH)-positive cells. The phenotype of FSH-R -/ - mice is reminiscent of human hypergonadotropic ovarian dysgenesis an d infertility.