title: Gonadotropin and kisspeptin gene expression, but not GnRH, are impaired in cFOS deficient mice.
abstract: cFOS is a pleiotropic transcription factor, which binds to the AP1 site in the promoter of target genes. In the pituitary gonadotropes, cFOS mediates induction of FSHβ and GnRH receptor genes. Herein, we analyzed reproductive function in the cFOS-deficient mice to determine its role in vivo. In the pituitary cFOS is necessary for gonadotropin subunit expression, while TSHβ is unaffected. Additionally, cFOS null animals have the same sex-steroid levels, although gametogenesis is impeded. In the brain, cFOS is not necessary for GnRH neuronal migration, axon targeting, cell number, or mRNA levels. Conversely, cFOS nulls, particularly females, have decreased Kiss1 neuron numbers and lower Kiss1 mRNA levels. Collectively, our novel findings suggest that cFOS plays a cell-specific role at multiple levels of the hypothalamic-pituitary-gonadal axis, affecting gonadotropes but not thyrotropes in the pituitary, and kisspeptin neurons but not GnRH neurons in the hypothalamus, thereby contributing to the overall control of reproduction.
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA; Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, San Diego, CA 92093-0674, USA.
authors.forename: Changchuan
authors.initials: C
authors.lastname: Xie
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Jonak
authors.affiliation: Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, San Diego, CA 92093-0674, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kauffman
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA. Electronic address: djurdjica.coss@ucr.edu.
authors.forename: Djurdjica
authors.initials: D
authors.lastname: Coss
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D016760:Proto-Oncogene Proteins c-fos; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: GnRH; Gonadotropin; Kisspeptin; c-Fos/AP-1; cFOS