Gonadotropin-releasing hormone receptor system: Modulatory role in aging and neurodegeneration

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 5, 2010, Pages 651-660

  Wang, Liyun ^a   Chadwick, Wayne ^a   Park, Sung Soo ^a   Zhou, Yu ^a   Silver, Nathan ^a   Martin, Bronwen ^a   Maudsley, Stuart ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Brain; Gnrh receptors; Gonadotropin releasing hormone; Hypothalamic pituitary gonadal axis; Neuron

Indexed keywords

GONADORELIN; GONADORELIN RECEPTOR; HORMONE;

AGING; ALZHEIMER DISEASE; ARTICLE; CENTRAL NERVOUS SYSTEM; HUMAN; HYPOTHALAMUS HYPOPHYSIS GONAD SYSTEM; NERVE DEGENERATION; NEUROPHYSIOLOGY; NONHUMAN; PATHOPHYSIOLOGY;

EID: 78649232879     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710793361559     Document Type: Article

References (157)

1. Millar, R.P.; Lu, Z.L.; Pawson, A.J.; Flanagan, C.A.; Morgan, K.; Maudsley, S.R. Gonadotropin-releasing hormone receptors. Endocr. Rev., 2004, 25, 235-275.
2. Caraty, A.; Locatelli, A. Effect of time after castration on secretion of LHRH and LH in the ram. J. Reprod. Fertil., 1988; 82, 263-269.
3. Jan Y.N.; Jan L.Y.; Kuffler S.W. A peptide as a possible transmitter in sympathetic ganglia of the frog. Proc. Natl. Acad. Sci. USA, 1979, 76, 1501-1505.
4. Cheung L.W.; Wong A.S. Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues. FEBS J., 2008, 275: 5479-5495.
5. Jan, Y.N.; Jan, L.Y.; Kuffler, S.W. Further evidence for peptidergic transmission in sympathetic ganglia. Proc Natl. Acad. Sci. USA, 1980, 77, 5008-5012.
6. Yang, SN.; Lu, F.; Wu, J.N.; Liu, D.D.; Hsieh, W.Y. Activation of gonadotropin-releasing hormone receptors induces a long-term enhancement of excitatory postsynaptic currents mediated by ionotropic glutamate receptors in the rat hippocampus. Neurosci. Lett. 1999, 260, 33-36.
7. Almeida, O.P.; Waterreus, A.; Spry, N.; Flicker, L.; Martins, RN. One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology, 2004, 29(8),1071-1081.
8. Gandy, S.; Almeida, O.P.; Fonte, J.; Lim, D.; Waterrus, A.; Spry, N.; Flicker, L.; Martins, R.N. Chemical andropause and amyloidbeta peptide. JAMA, 2001, 285, 2195-2196.
9. Troen BR. The biology of aging. Mt. Sinai J. Med., 2003, 70(1), 3-22.
10. Boulianne, G.L. Neuronal regulation of lifespan: clues from flies and worms. Mech. Ageing Dev., 2001, 122, 883-894.
11. Martin, B.; Golden, E.; Carlson, O.D.; Egan, J.M.; Mattson, M.P.; Maudsley, S. Caloric restriction: impact upon pituitary function and reproduction. Ageing Res. Rev., 2008, 7, 209-224.
12. Millar, R.P.; King, J.A.; Davidson, J.S. Milton, R.C. Gonadotrophin-releasing hormone--diversity of functions and clinical applications. S. Afr. Med. J., 1987, 72(11), 748-55.
13. Hsueh, A.J.; Schaeffer, J.M. Gonadotropin-releasing hormone as a paracrine hormone and neurotransmitter in extra-pituitary sites. J. Steroid. Biochem., 1985, 23, 757-764.
14. Jennes, L.; Conn, P.M. Gonadotropin-releasing hormone and its receptors in rat brain. Front. Neuroendocrinol., 1994, 15, 51-77.
15. Millar, R.P.; Lu, Z.L.; Pawson, A.J.; Flanagan, C.A.; Morgan, K.; Maudsley, S.R. Gonadotropin-releasing hormone receptors. Endocr. Rev., 2004, 25, 235-275.
16. Couzinet, B.; Schaison, G. The control of gonadotrophin secretion by ovarian steroids. Hum. Reprod., 1993, 8, 97-101.
17. Chakravarti, S.; Collins, W.P.; Forecast, J.D.; Newton, J.R.; Oram, D.H.; Studd, J.W. Hormonal profiles after the menopause. Br. Med. J., 1976, 2, 784-787.
18. Wide, L.; Nillius, S.J.; Gemzell, C.; Roos, P. Radioimmunosorbent assay of follicle-stimulating hormone and luteinizing hormone in serum and urine from men and women. Acta. Endocrinol. Suppl., 1973, 174, 3-58.
19. Neaves, W.B.; Johnson, L.; Porter, J.C.; Parker, C.R. Jr.; Petty, C.S. Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J. Clin. Endocrinol. Metab., 1984, 59, 756-763.
20. Nunomura, A.; Perry, G.; Aliev, G.; Hirai, K.; Takeda, A.; Balraj, E.K.; Jones, P.K.; Ghanbari, H.; Wataya, T.; Shimohama, S.; Chiba, S.; Atwood, C.S.; Petersen, R.B.; Smith, M.A. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol., 2001, 60, 759-767.
21. Ogawa, O.; Lee, H.G.; Zhu, X.; Raina, A.; Harris, P.L.; Castellani, R.J.; Perry, G.; Smith, M.A. Increased p27, an essential component of cell cycle control, in Alzheimer's disease. Aging Cell, 2003, 2, 105-110.
22. Harris, D.; Bonfil, D.; Chuderland, D.; Kraus, S.; Seger, R.; Naor, Z. Activation of MAPK cascades by GnRH: ERK and Jun N-terminal kinase are involved in basal and GnRH-stimulated activity of the glycoprotein hormone LHbeta-subunit promoter. Endocrinology, 2002, 143, 1018-1025.
23. Bowen, R.L.; Smith, M.A.; Harris, P.L.; Kubat, Z.; Martins, R.N.; Castellani, R.J.; Perry, G.; Atwood, C.S. Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology. J. Neurosci. Res., 2002, 70, 514-518.
24. Mattson MP, Maudsley S, Martin B. A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin. Ageing Res. Rev., 2004, 3(4), 445-64.
25. Powell, J.F.; Reska-Skinner, S.M.; Prakash, M.O.; Fischer, W.H.; Park, M.; Rivier, J.E.; Craig, A.G.; Mackie, G.O.; Sherwood, N.M. Two new forms of gonadotropin-releasing hormone in a protochordate and the evolutionary implications. Proc. Natl. Acad. Sci. USA, 1996, 93, 10461-10464.
26. Adams, B.A.; Tello, J.A.; Erchegyi, J.; Warby, C.; Hong, D.J.; Akinsanya, K.O.; Mackie, G.O.; Vale, W.; Rivier, J.E.; Sherwood, N.M. Six novel gonadotropin-releasing hormones are encoded as triplets on each of two genes in the protochordate, Ciona intestinalis. Endocrinology, 2003, 144, 1907-1919.
27. Badr, M.; Marchetti, B.; Pelletier, G. Changes in hippocampal LHRH receptor density during maturation and aging in the rat. Brain Res. Dev. Brain Res., 1989, 45(2), 179-184.
28. Badr, M.; Marchetti, B.; Pelletier, G. Modulation of hippocampal LHRH receptors by sex steroids in the rat. Peptides, 1988; 9(2), 441-442.
29. Ehret, G.; Buckenmaier, J. Estrogen-receptor occurrence in the female mouse brain: effects of maternal experience, ovariectomy, estrogen and anosmia. J. Physiol. Paris, 1994, 88(5), 315-329.
30. Adams, M.M.; Fink, S.E.; Shah, R.A.; Janssen, W.G.; Hayashi, S.; Milner, T.A.; McEwen, B.S.; Morrison, J.H. Estrogen and aging affect the subcellular distribution of estrogen receptor-alpha in the hippocampus of female rats. J. Neurosci., 2002, 22(9), 3608-3614.
31. Sar, M.; Lubahn, D.B.; French, F.S.; Wilson, E.M. Immunohistochemical localization of the androgen receptor in rat and human tissues. Endocrinology, 1990, 127(6), 3180-3186.
32. Xiao, L.; Jordan, C.L. Sex differences, laterality, and hormonal regulation of androgen receptor immunoreactivity in rat hippocampus. Horm. Behav., 2002, 42(3), 327-336.
33. Henderson, V.W.; Paganini-Hill, A.; Emanuel, C.K.; Dunn, M.E.; Buckwalter, J.G. Estrogen replacement therapy in older women: comparisons between Alzheimer's disease cases and nondemented control subjects. Arch. Neurol., 1994, 51, 896-900.
34. Tang, MX.; Jacobs, D.; Stern, Y.; Marder, K.; Schofield, P.; Gurland, B.; Andrews, H.; Mayeux, R. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet, 1996, 348, 429-432.
35. Fratiglioni, L., Viitanen, M., von Strauss, E.; Tontodonati, V.; Herlitz, A.; Winblad, B. Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the kungsholmen project, Stockholm. Neurology, 1997, 48, 132-138.
36. Stam, F.C.; Wigboldus, J.M.; Smeulders, A.W. Age incidence of senile brain amyloidosis. Pathol. Res. Pract., 1986, 181(5), 558-562.
37. Jorm, A.F.; Korten, A.E.; Henderson, A.S. The prevalence of dementia: A quantitative integration of the literature. Acta Psychiatr. Scand., 1987, 76, 465-479.
38. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA, 2002, 288, 321-333.
39. Bless E.P.; Walker, H.J.; Yu, K.W.; Knoll, J.G.; Moenter, S.M.; Schwarting, G.A.; Tobet S.A. Live view of gonadotropin-releasing hormone containing neuron migration. Endocrinology, 2005, 146, 463-468.
40. Song, T.; Nikolics, K.; Seeburg, P.H.; Goldsmith, P.C. GnRHprohormone-containing neurons in the primate brain: immunostaining for the GnRH-associated peptide. Peptides, 1987, 8, 335-346.
41. Kah, O.; Lethimonier, C.; Somoza, G.; Guilgur, LG.; Vaillant, C.; Lareyre JJ. GnRH and GnRH receptors in metazoa: A historical, comparative, and evolutive perspective. Gen. Comp. Endocrinol., 2007,153, 346-364.
42. Silver, M.R.; Kawauchi, H.; Nozaki, M.; Sower, SA. Cloning and analysis of the lamprey GnRH-III cDNA from eight species of lamprey representing the three families of Petromyzoniformes. Gen. Comp. Endocrinol., 2004,139, 85-94.
43. Suzuki, K.; Gamble, R.L.; Sower, S.A. Multiple transcripts encoding lamprey gonadotropin-releasing hormone-I precursore. J. Mol. Endocrinol., 2000, 24, 365-376.
44. Amemiya, Y.; Sogabe, Y.; Nozaki, M.; Takahashi, A.; Kawauchi, H. Somatolactin in the White Sturgeon and African Lungfish and Its Evolutionary Significance. Gen. Comp. Endocrinol., 1999, 114, 181-190.
45. Gorbman, A.; Sower, S.A. Evolution of the role of GnRH in animal (Metazoan) biology. Gen. Comp. Endocrinol., 2003, 134, 207-213.
46. Lescheid, D.W.; Terasawa, E.; Abler, L.A.; Urbanski, H.F.; Warby, C.M.; Millar, R.P.; Sherwood, N.M. A Second Form of Gonadotropin-Releasing Hormone (GnRH) with Characteristics of Chicken GnRH-II Is Present in the Primate Brain. Endocrinology, 1997, 138, 5618-5629.
47. Trinh, L.A.; McCutchen, M.D.; Bonner-Fraser, M.; Fraser, S.E.; Bumm, L.A.; McCauley, D.W. Fluorescent in situ hybridization employing the conventional NBT/BCIP chromogenic stain. Biotechniques, 2007, 42,756-759.
48. Millar, R.P.; Lowe, S.; Conklin, D.; Pawson, A.; Maudsley, S.; Troskie, B.; Ott, T.; Millar, M.; Lincoln, G.; Sellar, R.; Faurholm, B.; Scobie, G.; Kuestner, R.; Terasawa, E.; Katz, A. A novel mammalian receptor for the evolutionarily conserved type II gonadotropin-releasing hormone. Proc. Natl. Acad. Sci. USA, 2001, 98, 9636-9641.
49. Gault, P.M.; Maudsley, S.; Lincoln, G.A. Evidence that gonadotropin-releasing hormone II is not a physiological regulator of gonadotropin secretion in mammals. J. Neuroendocrinol., 2003, 15, 831-839.
50. Pawson, A.J.; Faccenda, E.; Maudsley, S.; Lu, Z.L.; Naor, Z.; Millar, R.P. Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization. Endocrinology, 2008, 149, 1415-1422.
51. Naor, Z. Signaling by G-protein-coupled receptor (GPCR): Studies on the GnRH receptor. Front. Neuroendocrinol., 2009, 30,10-29.
52. Mitchell, R.; Sim, P.J.; Leslie, T.; Johnson, M.S.; Thomson, F.J. Activation of MAP kinase associated with the priming effect of LHRH. J. Endocrinol., 1994, 140, 8-9.
53. Reiss, N.; Llevi, L.N.; Shacham, S.; Harris, D.; Seger, R.; Naor, Z. Mechanism of mitogen-activated protein kinase activation by gonadotropin-releasing hormone in the pituitary of alphaT3-1 cell line: differential roles of calcium and protein kinase C. Endocrinology, 1997, 138, 1673-1682.
54. Burger, L.L.; Haisenleder, D.J.; Dalkin, A.C.; Marshall, J.C. Regulation of gonadotropin subunit gene transcription. J. Mol. Endocrinol., 2004, 33, 559-584.
55. Haisenleder, DJ.; Yasin, M.; Dalkin, A.C.; Gilrain, C.; Marshall, J.C. GnRH regulates steroidogenic factor-1 (SF-1) gene expression in the rat pituitary. Endocrinology, 1996, 137, 5719-5722.
56. Kaiser, U.B.; Halvorson, L.M.; Chen, M.T. Sp1, steroidogenic factor 1 (SF-1), and early growth response protein 1 (egr-1) binding sites form a tripartite gonadotropin-releasing hormone response element in the rat luteinizing hormone-beta gene promoter: an integral role for SF-1. Mol. Endocrinol., 2000, 14(8), 1235-1245.
57. Borgeat, P.; Chavancy, G.; Dupont, A.; Labrie, F.; Arimura, A.; Schally, A.V. Stimulation of adenosine 30,50-cyclic monophosphate accumulation in anterior pituitary gland in vitro by synthetic luteinizing hormone-releasing hormone. Proc. Natl. Acad. Sci. USA, 1972, 69, 2677-2681.
58. Maudsley, S.; Davidson, L.; Pawson, A.J.; Chan, R.; López de Maturana, R.; Millar, R.P. Gonadotropin-releasing hormone (GnRH) antagonists promote proapoptotic signaling in peripheral reproductive tumor cells by activating a Galphai-coupling state of the type I GnRH receptor. Cancer Res., 2004, 64, 7533-7544.
59. Gardner, S.; Maudsley, S.; Millar, R.P.; Pawson, A.J. Nuclear stabilization of beta-catenin and inactivation of glycogen synthase kinase-3beta by gonadotropin-releasing hormone: targeting Wnt signaling in the pituitary gonadotrope. Mol. Endocrinol., 2007, 21, 3028-3038.
60. Davidson, L.; Pawson, A.J.; Millar, R.P.; Maudsley, S. Cytoskeletal reorganization dependence of signaling by the gonadotropin-releasing hormone receptor. J. Biol. Chem. 2004, 279, 1980-1993.
61. Maudsley, S.; Naor, Z.; Bonfil, D.; Davidson, L.; Karali, D.; Pawson, A.J.; Larder, R.; Pope, C.; Nelson, N.; Millar, R.P.; Brown, P. Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene. Mol. Endocrinol., 2007, 21, 1216-1233.
62. Davidson, L.; Pawson, A.J.; López de Maturana, R.; Freestone, S.H.; Barran, P.; Millar, R.P.; Maudsley, S. Gonadotropin-releasing hormone-induced activation of diacylglycerol kinase-zeta and its association with active c-Src. J. Biol. Chem., 2004, 279, 11906-11916.
63. Troskie, B.; King, J.A.; Millar, R.P.; Peng, Y.Y.; Kim, J.; Figueras, H.; Illing, N. Chicken GnRH II-like peptides and a GnRH receptor selective for chicken GnRH II in amphibian sympathetic ganglia. Neuroendocrinology, 1997, 65, 396-402.
64. Pawson, A.J.; Maudsley, S.; Morgan, K.; Davidson, L.; Naor, Z.; Millar, R.P. Inhibition of human type I gonadotropin-releasing hormone receptor (GnRHR) function by expression of a human type II GnRHR gene fragment. Endocrinology, 2005, 146, 2639-2649.
65. Berman, D.M.; Wilkie, T.M.; Gilman, A.G.; GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Cell, 1996, 86, 445-452.
66. Maudsley, S.; Davidson, L.; Pawson, A.J.; Freestone, S.H.; López de Maturana, R.; Thomson, A.A.; Millar, R.P. Gonadotropin releasing hormone functionally antagonizes testosterone activation of the human androgen receptor in prostate cells through focal adhesion complexes involving Hic-5. Neuroendocrinology, 2006, 84(5), 285-300.
67. Maudsley, S.; Pierce, K.L.; Zamah, A.M.; Miller, W.E.; Ahn, S.; Daaka, Y.; Lefkowitz, R.J.; Luttrell, L.M. The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor. J. Biol. Chem., 2000, 275, 9572-9580.
68. Shah, B.H.; Soh, J.W.; & Catt, K.J. Dependence of gonadotropin releasing hormone-induced neuronal MAPK signaling on epidermal growth factor receptor transactivation. J. Biol. Chem., 2003, 278, 2866-2875.
69. Shah, B.H.; Farshori, M.P.; Jambusaria, A.; Catt, K.J. Roles of Src and epidermal growth factor receptor transactivation in transient and sustained ERK1⁄2 responses to gonadotropin-releasing hormone receptor activation. J. Biol. Chem., 2003, 278, 19118-19126.
70. Kraus, S.; Benard, O.; Naor, Z.; Seger, R. c-Src is activated by the epidermal growth factor receptor in a pathway that mediates JNK and ERK activation by gonadotropin-releasing hormone in COS7 cells. J. Biol. Chem., 2003, 278, 32618-32630.
71. Haisenleder, D.J.; Cox, M.E.; Parsons, S.J.; Marshall, J.C. Gonadotropin-releasing hormone pulses are required to maintain activation of mitogen-activated protein kinase: role in stimulation of gonadotrope gene expression. Endocrinology, 1998, 139, 3104-3111.
72. Krsmanovic, L.Z.; Mores, N.; Navarro, C.E.; Arora, K.K.; Catt, K.J. An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion. Proc. Natl. Acad. Sci. USA, 2003, 100, 2969-2974.
73. Enomoto, M.; Seong, J.Y.; Kawashima, S.; Park, M.K. Proliferation of TSU-Pr1, a human prostatic carcinoma cell line is stimulated by gonadotropin-releasing hormone. Life Sci., 2004, 74, 3141-3152.
74. Loumaye, E.; Catt, K.J. Homologous regulation of gonadotropin-releasing hormone receptors in cultured pituitary cells. Science, 1982, 215, 983-985.
75. Cheung, L.W.; Leung, P.C.; Wong, A.S. Gonadotropin-releasing hormone promotes ovarian cancer cell invasiveness through c-jun NH2-terminal kinase-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9. Cancer Res., 2006, 66, 10902-10910.
76. Chen, CL.; Cheung, L.W.; Lau, M.T.; Choi, J.H.; Auersperg, N.; Wang, H.S.; Wong, A.S.; Leung, P.C. Differential role of gonadotropin-releasing hormone on human ovarian epithelial cancer cell invasion. Endocrine, 2007, 31, 311-320.
77. Arencibia, J.M.; Schally, A.V. Luteinizing hormone-releasing hormone as an autocrine growth factor in ES-2 ovarian cancer cell line. Int. J. Oncol., 2000,16, 1009-1013.
78. Enomoto, M.; Utsumi, M.; Park, M.K. Gonadotropin-releasing hormone induces actin cytoskeleton remodeling and affects cell migration in a cell-type-specific manner in TSU-Pr1 and DU145 cells. Endocrinology, 2006, 147, 530-542.
79. Maudsley, S.; Martin, B.; Luttrell, L.M. The origins of diversity and specificity in G protein-coupled receptor signaling. J. Pharmacol. Exp. Ther., 2005, 314, 485-494.
80. Liu, F.; Usui, I.; Evans, L.G.; Austin, D.A.; Mellon, P.L.; Olefsky, J.M.; Webster, N.J. Involvement of both G(q ⁄ 11) and G(s) proteins in gonadotropin-releasing hormone receptor-mediated signaling in L beta T2 cells. J. Biol. Chem., 2002, 277, 32099-32108.
81. Kraus, S.; Naor, Z.; Seger, R. Gonadotropin-releasing hormone in apoptosis of prostate cancer cells. Cancer Lett., 2006, 234, 109-123.
82. Imai, A.; Horibe, S.; Takagi, A.; Tamaya, T. Gi protein activation of gonadotropin-releasing hormone-mediated protein dephosphorylation in human endometrial carcinoma. Am. J. Obstet. Gynecol., 1997, 176, 371-376.
83. Raga, F.; Casan, EM.; Wen, Y.; Huang, HY.; Bonilla-Musoles, F.; Polan, ML. Independent regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-3 in human endometrial stromal cells by gonadotropin-releasing hormone: implications in early human implantation. J. Clin. Endocrinol. Metab., 1999, 84, 636-642.
84. Chou, C.S.; Zhu, H.; Shalev, E.; MacCalman, C.D.; Leung, P.C. The effects of gonadotrophin-releasing hormone (GnRH) I and GnRH II on the urokinase-type plasminogen activator inhibitor system in human extravillous cytotrophoblasts in vitro. J. Clin. Endocrinol. Metab., 2002, 87, 5594-5603.
85. Moretti, RM.; Montagnani Marelli, M.; Van Groeninghen, J.C.; Limonta, P. The effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human extravillous cytotrophoblasts in vitro. J. Clin. Endocrinol. Metab., 2002, 87, 3791-3797.
86. Moretti, R.M.; Monagnani Marelli, M.; van Groeninghen, J.C.; Motta, M.; Limonta, P. Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression. Endocr. Relat. Cancer, 2003,10, 161-167.
87. Choi, K.C.; Auersperg, N.; Leung, P.C. Expression and antiproliferative effect of a second form of gonadotropin-releasing hormone in normal and neoplastic ovarian surface epithelial cells. J. Clin. Endocrinol. Metab., 2001, 86(10), 5075-5078.
88. Kim, KY.; Choi, K.C.; Park, S.H.; Auersperg, N.; Leung, P.C. Extracellular signal-regulated protein kinase, but not c-Jun N-terminal kinase, is activated by type II gonadotrophin-releasing hormone involved in the inhibition of ovarian cancer cell proliferation. J. Clin. Endocrinol. Metab., 2005, 90, 1670-1677.
89. Rissman, E.F.; Li, X.; King, J.A.; Millar, R.P. Behavioral regulation of gonadotropin-releasing hormone production. Brain Res. Bull., 1997, 44(4), 459-464.
90. Emons, G.; Schally, A.V. The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. Hum. Reprod., 1994, 9(7), 1364-1379.
91. King, J.A.; Millar, R.P.; Vallarino, M.; Pierantoni, R. Localization and characterization of gonadotropin-releasing hormones in the brain, gonads, and plasma of a dipnoi (lungfish, Protopterus annectens). Regul. Pept., 1995, 57(2), 163-174.
92. Troskie, B.; King, J.A.; Millar, R.P.; Peng, Y.Y.; Kim, J.; Figueras, H.; Illing, N. Chicken GnRH II-like peptides and a GnRH receptor selective for chicken GnRH II in amphibian sympathetic ganglia. Neuroendocrinology, 1997, 65(6), 396-402.
93. Sower, S.A.; King, J.A.; Millar, R.P.; Sherwood, N.M.; Marshak, D.R. Comparative biological properties of lamprey gonadotropin-releasing hormone in vertebrates. Endocrinology, 1987, 120(2), 773-779.
94. Lovejoy, D.A.; Sherwood, N.M. Gonadotropin-releasing hormone in ratfish (Hydrolagus colliei): distribution between the sexes and possible relationship with chicken II and salmon II forms. Comp. Biochem. Physiol. B, 1989, 92(1), 111-118.
95. Hsueh, A.J.; Schaeffer, J.M. Gonadotropin-releasing hormone as a paracrine hormone and neurotransmitter in extra-pituitary sites. J. Steroid. Biochem., 1985, 23(5B), 757-64.
96. Jennes, L.; Conn, P.M. Gonadotropin-releasing hormone and its receptors in rat brain. Front. Neuroendocrinol., 1994, 15(1), 51-77.
97. Sealfon, S.C.; Weinstein, H.; Millar, R.P. Molecular mechanisms of ligand interaction with the gonadotropin-releasing hormone receptor. Endocr. Rev., 1997, 18, 180-207.
98. Wilson, A.C.; Salamat, M.S.; Haasl, R.J.; Roche, K.M.; Karande, A.; Meethal, S.V.; Terasawa, E.; Bowen, R.L.; Atwood, C.S. Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression. J. Endocrinol., 2006, 191, 651-663.
99. Kubek, M.; Wilber, J.F.; Leesthma, J. The identification of gonadotropin-releasing hormone (GnRH) in hypothalamic and extrahypothalamic loci of the human nervous system. Horm. Metab. Res., 1979, 11, 26-29.
100. He, D.; Funabashi, T.; Sano, A.; Uemura, T.; Minaguchi, H.; Kimura, F. Effects of glucose and related substrates on the recovery of the electrical activity of gonadotropin-releasing hormone pulse generator which is decreased by insulin-induced hypoglycemia in the estrogen-primed ovariectomized rat. Brain Res., 1999, 820, 71-76.
101. Lu, F.; Yang, J.M.; Wu, J.N.; Chen, Y.C.; Kao, Y.H.; Tung, C.S.; Yang, S.N. Activation of gonadotropin-releasing hormone receptors produces neuronal excitation in the rat hippocampus. Chin. J. Physiol., 1999, 42, 67-71.
102. Osada, T.; Kimura, F. LHRH effects on hippocampal-neurons are modulated by estrogen in rats. Endocr. J., 1995, 42, 251-257.
103. Gore, A.C.; Windsor-Engnell, B.M.; Terasawa, E. Menopausal increases in pulsatile gonadotropin-releasing hormone release in a nonhuman primate (Macaca mulatta). Endocrinology, 2004, 145, 4653-4659.
104. Atwood, C.S.; Meethal, S.V.; Liu, T.; Wilson, A.C.; Gallego, M.; Smith, M.A., Bowen, R.L. Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence. J. Neuropathol. Exp. Neurol., 2005, 64, 93-103.
105. Seong, J.; Park, S.; Kim, K. Enhanced splicing of the first intron from the gonadotropin-releasing hormone (GnRH) primary transcript is a prerequisite for mature GnRH messenger RNA: presence of GnRH neuronspecific splicing factors. Mol. Endocrinol., 1999, 13, 1882-1895.
106. Shim, C.; Khang, I.; Lee, K-A.; Kim, K. Expression and regulation of gonadotropin-relasing hormone (GnRH) and its receptor mRNA transcripts during mouse ovarian development. Korean J. Biol. Sci., 2005, 5, 217-224.
107. Jennes, L.; Woolums, S. Localization of gonadotropin releasing hormone receptor mRNA in rat brain. Endocrine, 1994, 2, 521-528.
108. Jennes, L.; Dalati, B.; Conn, P.M. Distribution of gonadotropin releasing hormone agonist binding sites in the rat central nervous system. Brain Res., 1988, 452, 156-164.
109. Renaud, L.P.; Martin, J.B.; Brazeau, P. Depressant action of TRH, LH-RH and somatostatin on activity of central neurones. Nature, 1975, 255, 233-235.
110. Renaud, L.P.; Martin, J.B.; Brazeau, P. Hypothalamic releasing factors: physiological evidence for a regulatory action on central neurons and pathways for their distribution in brain. Pharmacol. Biochem. Behav., 1976, 5, 171-178.
111. Quintanar, J.L.; Salinas, E. Neurotrophic effects of GnRH on neurite outgrowth and neurofilament protein expression in cultured cerebral cortical neurons of rat embryos. Neurochem. Res., 2008, 33, 1051-1056.
112. King, J.A.; Millar, R.P. Identification of His5,Trp7,Tyr8-GnRH (chicken GnRH II) in amphibian brain. Peptides, 1986, 7(5), 827-834.
113. Maney, D.L.; Richardson, R.D.; Wingfield, J.C. Central administration of chicken gonadotropin-releasing hormone-II enhances courtship behavior in a female sparrow. Horm. Behav., 1997, 32(1), 11-18.
114. Temple, J.L.; Millar, R.P.; Rissman, E.F. An evolutionarily conserved form of gonadotropin-releasing hormone coordinates energy and reproductive behavior. Endocrinology, 2003, 144(1), 13-19.
115. Jones, S.W. Chicken II luteinizing hormone-releasing hormone inhibits the M-current of bullfrog sympathetic neurons. Neurosci. Lett., 1987, 80, 180-184.
116. Darby, S.; Stockley, J.; Khan, M.M.; Robson, C.N.; Leung, H.Y.; Gnanapragasam, V.J. Expression of GnRH type II is regulated by the androgen receptor in prostate cancer. Endocr. Relat. Cancer, 2007, 14(3), 613-624.
117. Emons, G.; Schröder, B.; Ortmann, O.; Westphalen, S.; Schulz, K.D.; Schally, A.V. High affinity binding and direct antiproliferative effects of luteinizing hormone-releasing hormone analogs in human endometrial cancer cell lines. J. Clin. Endocrinol. Metab., 1993, 77(6), 1458-1464.
118. Morgan, K.; Conklin, D.; Pawson, A.J.; Sellar, R.; Ott, T.R.; Millar, R.P. A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12. Endocrinology, 2003, 144, 423-436.
119. López de Maturana, R.; Pawson, A.J.; Lu, Z.L.; Davidson, L.; Maudsley, S.; Morgan, K.; Langdon, S.P.; Millar, R.P. Gonadotropin-releasing hormone analog structural determinants of selectivity for inhibition of cell growth: support for the concept of ligand-induced selective signaling. Mol. Endocrinol., 2008, 22(7), 1711-1722.
120. Cummings, J.L. Treatment of Alzheimer's disease: current and future therapeutic approaches. Rev. Neurol. Dis., 2004, 1, 60-69.
121. Braak, H.; Rüb, U.; Schultz, C.; Del Tredici, K. Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases. J. Alzheimers Dis., 2006, 9, 35-44.
122. Price, J.L.; Davis, P.B.; Morris, J.C.; White, D.L. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol. Aging, 1991, 12, 295-312.
123. Kihara, T.; Shimohama, S.; Sawada, H.; Kimura, J.; Kume, T.; Kochiyama, H.; Maeda, T.; Akaike, A. Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann. Neurol., 1997, 42, 159-163.
124. Maudsley, S.; Mattson, M.P. Protein twists and turns in Alzheimer disease. Nat. Med., 2006, 12, 392-393.
125. Yao, Y.; Clark, C.M.; Trojanowski, J.Q.; Lee, V.M.; Praticò, D. Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment. Ann. Neurol., 2005, 58, 623-626.
126. Hsiao, K.; Chapman, P.; Nilsen, S.; Eckman, C.; Harigaya, Y.; Younkin, S.; Yang, F.; Cole, G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science, 1996, 274(5284), 99-102.
127. van Groen, T.; Kiliaan, A.J.; Kadish, I. Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice. Neurobiol. Dis., 2006, 23(3), 653-62.
128. Nelson, R.L.; Guo, Z.; Halagappa, V.M.; Pearson, M.; Gray, A.J.; Matsuoka, Y.; Brown, M.; Martin, B.; Iyun, T.; Maudsley, S.; Clark, R.F.; Mattson, M.P. Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. Exp. Neurol., 2007, 205, 166-176.
129. Martin, B.; Brenneman, R.; Becker K.G.; Gucek, M.; Cole, R.N.; Maudsley, S. iTRAQ analysis of complex proteome alterations in 3xTgAD Alzheimer's mice: understanding the interface between physiology and disease. PLoS One, 2008, 3(7), e2750.
130. Kumar-Singh, S.; Theuns, J.; Van Broeck, B.; Pirici, D.; Vennekens, K.; Corsmit, E.; Cruts, M.; Dermaut, B.; Wang, R.; Van Broeckhoven, C. Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum. Mutat., 2006, 27, 686-695.
131. Luheshi, L.M.; Tartaglia, G.G.; Brorsson, A.C.; Pawar, A.P.; Watson, I.E.; Chiti, F.; Vendruscolo, M.; Lomas, D.A.; Dobson, C.M.; Crowther, D.C. Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity. PLoS Biol., 2007, 5, e290.
132. Roychaudhuri, R.; Yang, M.; Hoshi, M.M.; Teplow, D.B. Amyloid beta-protein assembly and Alzheimer disease. J. Biol. Chem., 2009, 284, 4749-4753.
133. Deshpande, A.; Mina, E.; Glabe, C.; Busciglio, J. Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J. Neurosci., 2006, 26, 6011-6018.
134. Shankar, G.M.; Li, S.; Mehta, T.H.; Garcia-Munoz, A.; Shepardson, N.E.; Smith, I.; Brett, F.M.; Farrell, M.A.; Rowan, M.J.; Lemere, C.A.; Regan, C.M.; Walsh, D.M.; Sabatini, B.L.; Selkoe, D.J. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med., 2008, 14, 837-842.
135. Selkoe DJ. Aging, amyloid, and Alzheimer's disease: a perspective in honor of Carl Cotman. Neurochem. Res., 2003, 28(11), 1705-1713.
136. Selkoe, D.J. Alzheimer's disease: genotypes, phenotypes, and treatments. Science, 1997, 275, 630-631.
137. Savonenko, A.V.; Xu, G.M.; Price, D.L.; Borchelt, D.R.; Markowska, A.L. Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APPSWE. Neurobiol. Dis., 2003, 12, 194-211.
138. Takeuchi, A.; Irizarry, M.C.; Duff, K.; Saido, T.C.; Hsiao Ashe, K.; Hasegawa, M.; Mann, D.M.; Hyman, B.T.; Iwatsubo, T. Age-related amyloid deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid precursor protein Swedish mutant is not associated with global neuronal loss. Am. J. Pathol., 2000, 157, 331-339.
139. Perry, G.; Nunomura, A.; Raina, A.K.; Smith, M.A. Amyloidjunkies. Lancet, 2000, 355, 757.
140. Obrenovich, M.E.; Joseph, J.A.; Atwood, C.S.; Perry, G.; Smith, M.A. Alzheimer's disease-a new beginning, or a final exit? Edited by Copani A. NF. TX: Landes Biosci., 2003.
141. Rottkamp, C.A.; Atwood, C.S.; Joseph, J.A.; Nunomura, A.; Perry, G.; Smith, M.A. The state versus amyloid-: the trial of the most wanted criminal in Alzheimer disease. Peptides, 2002, 23, 1333-1341.
142. Manly, J.J.; Merchant, C.A.; Jacobs, D.M.; Small, S.A.; Bell, K.; Ferin, M.; Mayeux, R. Endogenous estrogen levels and Alzheimer's disease among postmenopausal women. Neurology, 2000, 54, 833-837.
143. Rapp, S.R.; Espeland, M.A.; Shumaker, S.A.; Henderson, V.W.; Brunner, R.L.; Manson, J.E.; Gass, M.L.; Stefanick, M.L.; Lane, D.S.; Hays, J.; Johnson, K.C.; Coker, L.H.; Dailey, M.; Bowen, D. WHIMS Investigators. JAMA, 2003, 289, 2663-2672.
144. Jennes, L.; Brame, B.; Centers, A.; Janovick, J.A.; Conn, P.M. Regulation of hippocampal gonadotropin releasing hormone (GnRH) receptor mRNA and GnRH-stimulated inositol phosphate production by gonadal steroid hormones. Brain Res. Mol. Brain Res., 1995, 33, 104-110.
145. Thompson, T.L.; Moss, R.L. Specific binding of 125ILHRH agonist to hippocampal membranes: fluctuations during the estrous cycle. Peptides, 1992, 13, 891-896.
146. Redding, T.W.; Kastin, A.J.; Gonzales-Barcena, D.; Coy, D.H.; Coy, E.J.; Schalch, D.S.; Schally, A.V. The half-life, metabolism and excretion of tritiated luteinizing hormone-releasing hormone (LH-RH) in man. J. Clin. Endocrinol. Metab., 1973, 37(4), 626-631.
147. Fauconnier, J.P.; Teuwissen, B.; Thomas, K. Rate of disappearance in plasma of synthetic LH-RH intravenously injected in man. Gynecol. Obstet. Invest., 1978, 9(5), 229-237.
148. Bowen, R.L.; Isley, J.P.; Atkinson, R.L. An association of elevated serum gonadotropin concentrations and Alzheimer disease? J. Neuroendocrinol., 2000, 12, 351-354.
149. Short, S.M.; Boyer, J.L.; Juliano, R.L. Integrins regulate the linkage between upstream and downstream events in G protein-coupled receptor signaling to mitogen-activated protein kinase. J. Biol. Chem., 2000, 275, 12970-12977.
150. Yang, S.N.; Lu, F.; Wu, J.N.; Liu, D.D.; Hsieh, W.Y. Activation of gonadotropin-releasing hormone receptors induces a long-term enhancement of excitatory postsynaptic currents mediated by ionotropic glutamate receptors in the rat hippocampus. Neurosci. Lett., 1999, 260, 33-36.
151. Prange-Kiel, J.; Jarry, H.; Schoen, M.; Kohlmann, P.; Lohse, C.; Zhou, L.; Rune, G.M. Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis. J. Cell. Biol., 2008, 180, 417-426.
152. Casadesus, G.; Webber, K.M.; Atwood, C.S.; Pappolla, M.A.; Perry, G.; Bowen, R.L.; Smith, M.A. Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice. Biochim. Biophys. Acta., 2006, 1762(4), 447-452.
153. Vadakkadath Meethal, S.; Atwood, C.S. Alzheimer's disease: the impact of age-related changes in reproductive hormones. Cell Mol. Life Sci., 2005, 62(3), 257-270.
154. Wang, L.; Martin, B.; Brenneman, R.; Luttrell, L.M.; Maudsley, S. Allosteric modulators of G protein-coupled receptors: future therapeutics for complex physiological disorders. J. Pharmacol. Exp. Ther., 2009, 331(2), 340-348.
155. López de Maturana, R.; Martin, B.; Millar, R.P.; Brown, P.; Davidson, L.; Pawson, A.J.; Nicol, M.R.; Mason, J.I.; Barran, P.; Naor, Z.; Maudsley, S. GnRH-mediated DAN production regulates the transcription of the GnRH receptor in gonadotrope cells. Neuromol. Med., 2007, 9(3), 230-248.
156. Maudsley, S.; Martin, B.; Luttrell, L.M. G protein-coupled receptor signaling complexity in neuronal tissue: implications for novel therapeutics. Curr. Alzheimer Res., 2007, 4(1), 3-19.
157. rd; Ladenheim, B.; Cadet, J.L.; Maudsley, S. Growth factor signals in neural cells: coherent patterns of interaction control multiple levels of molecular and phenotypic responses. J. Biol. Chem., 2009, 284(4), 2493-2511.