title: The gonadotropin-releasing hormone (GnRH) neuronal population is normal in size and distribution in GnRH-deficient and GnRH receptor-mutant hypogonadal mice.
abstract: Hypothalamic GnRH neurons are essential for initiation and regulation of reproductive function. In addition to pituitary gonadotrope stimulation, activity of GnRH through its receptor (GnRHR) has been suggested to include autocrine regulation of the GnRH neuron. Two hypogonadal mouse strains, the Gnrh1 mutant (hpg) mice and Gnrhr mutant mice were used to investigate the potential role of GnRH signaling in the proper development and maintenance of GnRH neurons. Immunocytochemical analysis of heterozygous hpg mice revealed a GnRH neuron population that was normal in size and distribution, indicating no effect from reduced Gnrh1 gene dosage on the neurons themselves. To visualize GnRH neurons in homozygous GnRH-deficient hpg mice, heterozygous hpg mice were crossed with GnRH-green fluorescent protein (GFP) transgenic mice with targeted expression of the GFP reporter gene in GnRH neurons. Analysis of forebrains of homozygous hpg/GFP-positive mice immunostained for GFP revealed a normal population size and appropriate distribution of GnRH neurons in hpg mice, with immunoreactive neuronal processes present at the median eminence. Similarly, adult mice deficient in functional GnRHR possessed a full complement of GnRH neurons in the basal forebrain that was indistinguishable from the distribution of GnRH neurons in their wild-type counterparts. Moreover, hpg/GFP neurons retained the ability to generate spontaneous bursts of action potential firing activity, suggesting that GnRH peptide is not required for this function. These data establish that autocrine-paracrine GnRH-signaling is not a prerequisite for the developmental migration of GnRH neurons into the brain or for the projection of GnRH neurosecretory axons.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Gill
authors.forename: Brandon
authors.initials: B
authors.lastname: Wadas
authors.forename: Peilin
authors.initials: P
authors.lastname: Chen
authors.forename: Wendy
authors.initials: W
authors.lastname: Portillo
authors.forename: Andrea
authors.initials: A
authors.lastname: Reyna
authors.forename: Elisa
authors.initials: E
authors.lastname: Jorgensen
authors.forename: Shaila
authors.initials: S
authors.lastname: Mani
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Schwarting
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Moenter
authors.forename: Stuart
authors.initials: S
authors.lastname: Tobet
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000235:genetics; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics; D048429:Cell Size; D004594:Electrophysiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007006:Hypogonadism / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008954:Models, Biological; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D019899:Paracrine Communication / Q000235:genetics; D011966:Receptors, LHRH / Q000235:genetics* / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D011966:Receptors, LHRH; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone