Abstract
The gonadotropin-releasing hormone (GnRH) neurons have represented something of an enigma ever since the isolation of the decapeptide in 1971 (1,2) and the first immunocytochemical mappings of their location within the mammalian forebrain shortly thereafter (3,4). Unusually, they were not found to exist within any defined nucleus or subregion of the brain but, instead, were identified as a scattered continuum of neurons within the basal forebrain. This was found to occur in all mammalian brains, although the relative distribution of GnRH neurons along the “pathway” from the olfactory lobes to the basal hypothalamus differs (4). It now seems most likely that this peculiar distribution arises from the extraordinary migration of the GnRH neurons from the olfactory placode into the brain during embryogenesis (4,5,6). However, it remains that the scattered nature of GnRH phenotype has made the detailed molecular and cellular investigation of these neurons extremely difficult. Given the critical role of these cells in the neural regulation of fertility, this has been unfortunate. While many strategies have been attempted to facilitate the characterisation of the GnRH phenotype, the most successful to date has been through the use of transgenics. I intend here to review these various transgenic strategies and suggest what we might expect from them in the near future.
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References
Amoss M, Bunges R, Blackwell R, Vale W, Fellows R, Guillemin R. Purification, amino acid composition and N-terminus of the hypothalamic luteinizing hormone releasing hormone factor (LRF) of ovine origin. Biochem Biophys Res Comm 1971;44: 205–210.
Schally AV, Arimura A, Baker Y. Isolation and properties of the FSH and LH-releasing hormone. Biochem Biophys Res Comm 1971;43:393–399.
Barry J, DuBois MP, Poulain P. LRF producing cells of the mammalian hypothalamusZ.Zellforsch 1973;146:351–366.
Silverman A, Livne I, Witkin JW. The gonadotrophin-releasing hormone (GnRH) neuronal systems: hybridization. In: The Physiology of Reproduction (Eds: Knobil E & Neill JD) pp1683–1706. New York: Raven 1994.
Schwanzel-Fukuda M, Pfaff DW. Origin of luteinizing hormone-releasing neurons. Nature 1989;338:161–164.
Wray S, Grant P, Gainer H. Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode. Proc Natl Acad Sci USA 1989;86:8132–8136.
Mason AJ, Pitts SL, Nikolics K, Szonyi E, Wilcox JN, Seeburg PH, Stewart, TA. The hypogonadal mouse: Reproductive functions restored by gene therapy. Science 1986;234:1372–1378.
Mellon PL, Windle JJ, Goldsmith PC, Padula CA, Roberts JL,Weiner RI. Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 1990;5:1–10.
Radovick S, Wray S, Lee E, Nichols DK, Nakayama Y, Weintraub BD, Westphal H, Cutler GB, Wondisford FE. Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice. Proc Natl Acad Sci USA 1991;88:3402–3406.
Weiner RI, Wetsel W, Goldsmith P, Escalera de la Martinez G, Windle J, Padula C, Choi A, Negro-Vilar A, Mellon P. Gonadotropin-releasing hormone neuronal cell lines. Front Neuroendocrinol 1992;13:119.
Turgeon JL. Gonadotropin-releasing hormone neuron cell biology. TEM 1996;7:55–56.
Zhen S., Dunn IC., Wray S., Liu Y., Chappell PE., Levine JE., Radovick S. An alternative gonadotropin-releasing hormone (GnRH) RNA splicing product found in cultured GnRH neurons and mouse hypothalamus. J Biol Chem 1997;272:12620–12625
Krsmanovic LZ, Stojilkovic SS, Catt KJ. Pulsatile gonadotropin-releasing hormone release and its regulation. TEM 1996;7:56–59.
Wierman ME, Fang Z, Kepa JK. GnRH gene expression in neuronal cell lines. TEM 1996;7:60–65.
Nelson SB, Eraly SA, Mellon PL. The GnRH promoter: target of transcription factors, hormones, and signaling pathways. Mol Cell Endocrinol 1998;140:51–155.
Selmanoff M. Commentary on the use of immortalized neuroendocrine cell lines for physiological research. Endocrine 1997; 6:1–3.
Waschek JA. Transgenic targeting of neuroendocrine peptide genes in the hypothalamic-pituitary axis. Mol Neurobiol 1995;10:217.
Lira SA, Crenshaw III EB, Glass CK, Swanson LW, Rosenfeld MG. Identification of rat growth hormone genomic sequences targeting pituitary expression in transgenic mice. Proc Natl Acad Sci USA 1988;85:4755–4759.
Rubinstein M, Liu B, Goodman RH, Low MJ. Targeted expression of somatostatin in vasopressinergic magnocellular hypothalamic neurons of transgenic mice. Mol Cell Neurosci 1992;3:152–161.
Wolfe AM., Wray S, Westphal H, Radovick S. Cell-specific expression of the human gonadotropin-releasing hormone gene in transgenic animals. J Biol Chem 1996;271:20018–20023.
Skynner MJ, Slater R, Sim JS, Allen ND, Herbison AE. Promoter transgenics reveal multiple gonadotropin-releasing hormone-1 -expressing cell populations of different embryological origin in mouse brain. J Neurosci 1999;19:5955–5966.
Pape J-R, Skynner MJ, Allen ND, Herbison AE. Transgenics identify distal 5’- and 3’ sequences specifying gonadotropin-releasing hormone expression in adult mice. Mol Endocrinol 1999;13:2203–2211.
Spergel DJ, Krueth U, Hanley DF, Sprengel R, Seeburg PH. GNRH/LACZ mice exhibit two major populations of beta-galactosidase-stained neurons. Soc Neurosci Abst 1998;24:237.9.
Wu TJ, Gibson MJ, Silverman AJ. Gonadotropin-releasing hormone (GnRH) neurons of the developing tectum of the mouse. J Neuroendocrinol 1995;7:899–902.
Quinn W. Neuronal-specific gene expression-The interaction of both positive and negative transcriptional regulators. Prog Neurobiol 1996;50:363–379.
Spergel DJ, Kruth U, Hanley DF. Sprengel R, Seeburg PH. GABA-and glutamate-activated channels in green fluorescent protein-tagged gonadotropin-releasing hormone neurone in transgenic mice. J Neurosci 1999;19:2037–2050.
Suter ICJ, Song WJ, Sampson TL, Wuarin J-P, Saunders JT, Dudek FE, Moenter SM.. Genetic targeting of green fluorescent protein to gonadotropin-releasing hormone neurons: characterization of whole-cell electrophysiological properties and morphology. Endocrinology 1999;141:412–419.
Zhang Y-Z, Naleway JJ, Larison KD, Huang Z, Haugland RP. Detecting lacZ gene expression in living cells with new lipophilic, fluorogenic ß-galactosidase substrates. FASEB J 1991; 5:3108–3113.
Skynner MJ, Sim JS, Herbison AE. Detection of estrogen receptor a and ß messenger ribonucleic acids in adult gonadotropin-releasing hormone neurons. Endocrinology 1999;140:115195–5201.
Sim JA, Skynner MJ, Dyer RG, Herbison AE. Patch-clamp studies on GnRH neurons in acute slice preparations. Soc Neurosci Abst 1998;24:827.4.
Postigo H, Weiner R, Moenter S, Zhang L, Tsai P. Characterization of transgenic mice overexpressing a dominant negative FGF receptor in GnRH neurons. Soc Neurosci Abst 1999;25:777.4.
Tsien JZ, Chen DF, Gerber D, Tom C, Mercer EH, Anderson DJ, Mayford M, Kandel ER, Tonegawa S. Subregion-and cell type-restricted gene knockout in mouse brain. Cell 1996;87:1317–1326.
Gibson MJ, Miller GM, Silverman AJ. Pulsatile luteinizing hormone secretion in normal female mice and in hypogonadal female mice with preoptic area implants. Endocrinology 1991;128:965–971.
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Herbison, A.E. (2001). GnRH Transgenic Models. In: Castro, M.G. (eds) Transgenic Models in Endocrinology. Endocrine Updates, vol 13. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1633-0_3
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DOI: https://doi.org/10.1007/978-1-4615-1633-0_3
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