Hormonal regulation of clonal, immortalized hypothalamic neurons expressing neuropeptides involved in reproduction and feeding

Molecular Neurobiology

Volumn 35, Issue 2, 2007, Pages 182-194

  Belsham, Denise D ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY HEALTH NETWORK   (Canada)

Author keywords

Estrogen; Hypothalamus; Leptin; Neuropeptide Y; Neurotensin

Indexed keywords

ESTROGEN; LEPTIN; NEUROPEPTIDE; NEUROPEPTIDE Y; NEUROTENSIN;

CELL CLONING; CELL IMMORTALIZATION; FEEDING; GENE TRANSFER; HORMONAL REGULATION; HUMAN; HYPOTHALAMUS; NERVE CELL; NONHUMAN; ONCOGENE; REPRODUCTION; REVIEW; SIGNAL TRANSDUCTION;

EID: 36248985638     PISSN: 08937648     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12035-007-0010-5     Document Type: Review

References (129)

1. Everitt BJ, Hokfelt T (1990) Neuroendocrine anatomy of the hypothalamus. Acta Neurochir Suppl (Wien) 47:1-15
2. Kopelman PG (2000) Obesity as a medical problem. Nature 404:635-643
3. Marx J (2003) Cellular warriors at the battle of the bulge. Science 299:846-849
4. Friedman JM (2003) A war on obesity, not the obese. Science 299:856-858
5. Wade GN, Gray JM, Bartness TJ (1985) Gonadal influences on adiposity. Int J Obes 9(Suppl 1):83-92
6. Cooke PS, Naaz A (2004) Role of estrogens in adipocyte development and function. Exp Biol Med (Maywood) 229:1127-1135
7. Hoffman GE, Smith MS, Verbalis JG (1993) c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. Front Neuroendocrinol 14:173-213
8. Dufourny L, Warembourg M, Jolivet A (1999) Quantitative studies of progesterone receptor and nitric oxide synthase colocalization with somatostatin, or neurotensin, or substance P in neurons of the guinea pig ventrolateral hypothalamic nucleus: an immunocytochemical triple-label analysis. J Chem Neuroanat 17:33-43
9. Elmquist JK, Elias CF, Saper CB (1999) From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22:221-232
10. Smith MS, Grove KL (2002) Integration of the regulation of reproductive function and energy balance: lactation as a model. Front Neuroendocrinol 23:225-256
11. Cepko CL (1989) Immortalization of neural cells via retrovirus-mediated oncogene transduction. Annu Rev Neurosci 12:47-65
12. Augusti-Tocco G, Sato G (1969) Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc Natl Acad Sci U S A 64:311-315
13. De Vitry F, Camier M, Czernichow P, Benda P, Cohen P, Tixier-Vidal A (1974) Establishment of a clone of mouse hypothalamic neurosecretory cells synthesizing neurophysin and vasopressin. Proc Natl Acad Sci U S A 71:3575-3579
14. Mellon PL, Windle JJ, Goldsmith PC, Padula CA, Roberts JL, Weiner RI (1990) Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 5:1-10
15. Zakaria M, Dunn IC, Zhen S, Su E, Smith E, Patriquin E, Radovick S (1996) Phorbol ester regulation of the gonadotropin-releasing hormone (GnRH) gene in GnRH-secreting cell lines: a molecular basis for species differences. Mol Endocrinol 10:1282-1291
16. Earnest DJ, Liang FQ, DiGiorgio S, Gallagher M, Harvey B, Earnest B, Seigel GM (1999) Establishment and characterization of adenoviral E1A immortalized cell lines derived from the rat suprachiasmatic nucleus. J Neurobiol 39:1-13
17. Radovick S, Wray S, Lee E, Nicols DK, Nakayama Y, Weintraub BD, Westphal H, Cutler GB Jr, Wondisford FE (1991) Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice. Proc Natl Acad Sci U S A 88:3402-3406
18. Wetsel WC (1995) Immortalized hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons: a new tool for dissecting the molecular and cellular basis of LHRH physiology. Cell Mol Neurobiol 15:43-78
19. Mahachoklertwattana P, Sanchez J, Kaplan SL, Grumbach MM (1994) N-methyl-D-aspartate (NMDA) receptors mediate the release of gonadotropin-releasing hormone (GnRH) by NMDA in a hypothalamic GnRH neuronal cell line (GT1-1). Endocrinology 134:1023-1030
20. 2+]i and gonadotropin-releasing hormone secretion in immortalized hypothalamic GT1-7 neurons. Neuroendocrinology 59:309-317
21. Belsham DD, Wetsel WC, Mellon PL (1996) NMDA and nitric oxide act through the cGMP signal transduction pathway to repress hypothalamic gonadotropin-releasing hormone gene expression. EMBO J 15:538-547
22. Brann DW, Mahesh VB (1995) Glutamate: a major neuroendocrine excitatory signal mediating steroid effects on gonadotropin secretion. J Steroid Biochem Mol Biol 53:325-329
23. Brann DW, Zamorano PL, De Sevilla L, Mahesh VB (2005) Expression of glutamate receptor subunits in the hypothalamus of the female rat during the afternoon of the proestrous luteinizing hormone surge and effects of antiprogestin treatment and aging. Neuroendocrinology 81:120-128
24. Gyurko R, Leupen S, Huang PL (2002) Deletion of exon 6 of the neuronal nitric oxide synthase gene in mice results in hypogonadism and infertility. Endocrinology 143:2767-2774
25. Krsmanovic LZ, Stojilkovic SS, Balla T, al Damluji S, Weiner RI, Catt KJ (1991) Receptors and neurosecretory actions of endothelin in hypothalamic neurons. Proc Natl Acad Sci U S A 88:11124-11128
26. Martinez de la Escalera G, Choi AL, Weiner RI (1992) β1-adrenergic regulation of the GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines: stimulation of GnRH release via receptors positively coupled to adenylate cyclase. Endocrinology 131:1397-1402
27. Martinez de la Escalera G, Gallo F, Choi AL, Weiner RI (1992) Dopaminergic regulation of the GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines: stimulation of GnRH release via D1-receptors positively coupled to adenylate cyclase. Endocrinology 131:2965-2971
28. Moretto M, Lopez FJ, Negro-Vilar A (1993) Nitric oxide regulates luteinizing hormone-releasing hormone secretion. Endocrinology 133:2399-2402
29. Rettori V, Belova N, Dees WL, Nyberg CL, Gimeno M, McCann SM (1993) Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro. Proc Natl Acad Sci U S A 90:10130-10134
30. Krsmanovic LZ, Stojilkovic SS, Mertz LM, Tomic M, Catt KJ (1993) Expression of gonadotropin-releasing hormone receptors and autocrine regulation of neuropeptide release in immortalized hypothalamic neurons. Proc Natl Acad Sci U S A 90:3908-3912
31. Whyte DB, Lawson MA, Belsham DD, Eraly SA, Bond CT, Adelman JP, Mellon PL (1995) A neuron-specific enhancer targets expression of the gonadotropin-releasing hormone gene to hypothalamic neurosecretory neurons. Mol Endocrinol 9:467-477
32. ClarkME,Mellon PL (1995) The POU homeodomain transcription factor Oct-1 is essential for activity of the gonadotropin-releasing hormone neuron-specific enhancer. Mol Cell Biol 15:6169-6177
33. Lawson MA, Whyte DB, Mellon PL (1996) GATA factors are essential for activity of the neuron-specific enhancer of the gonadotropin-releasing hormone gene. Mol Cell Biol 16:3596-3605
34. Lawson MA, Buhain AR, Jovenal JC, Mellon PL (1998) Multiple factors interacting at the GATA sites of the gonadotropin-releasing hormone neuron-specific enhancer regulate gene expression. Mol Endocrinol 12:364-377
35. Belsham DD, Mellon PL (2000) Transcription factors Oct-1 and C/EBP b (CCAAT/enhancer-binding protein-b) are involved in the glutamate/nitric oxide/cyclic-guanosine 5′-monophosphate-mediated repression of mediated repression of gonadotropinreleasing hormone gene expression. Mol Endocrinol 14:212-228
36. Belsham DD, Evangelou A, Roy D, Duc VL, Brown TJ (1998) Regulation of gonadotropin-releasing hormone gene expression by 5α-dihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons. Endocrinology 139:1108-1114
37. Wetsel WC, Eraly SA, Whyte DB, Mellon PL (1993) Regulation of gonadotropin-releasing hormone by protein kinases A and C in immortalized hypothalamic neurons. Endocrinology 132:2360-2370
38. Yu KL, Yeo TT, Dong KW, Jakubowski M, Lackner-Arkin C, Blum M, Roberts JL (1994) Second messenger regulation of mouse gonadotropin-releasing hormone gene expression in immortalized mouse hypothalamic GT1-3 cells. Mol Cell Endocrinol 102:85-92
39. Bruder JM, Drebs WD, Nett TM, Wierman ME (1992) Phorbol ester activation of the protein kinase C pathway inhibits gonadotropin-releasing hormone gene expression. Endocrinology 131:2552-2558
40. Eraly SA, Mellon PL (1995) Regulation of gonadotropin-releasing hormone transcription by protein kinase C is mediated by evolutionarily conserved, promoter-proximal elements. Mol Endocrinol 9:848-859
41. Eraly S, Nelson S, Huang K, Mellon P (1998) Oct-1 binds promoter elements required for transcription of the GnRH gene. Mol Endocrinol 12:469-481
42. Roy D, Angelini N, Belsham DD (1999) Estrogen directly represses gonadotropin-releasing hormone (GnRH) mRNA synthesis in GT1-7 GnRH-secreting hypothalamic neurons expressing estrogen receptor (ER) a and ERb. Endocrinology 140:5045-5053
43. Roy D, Angelini N, Frieda H, Brown GM, Belsham DD (2001) Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin. Endocrinology 142:4711-4720
44. Roy D, Belsham DD (2002) Melatonin receptor activation regulates gonadotropin-releasing hormone (GnRH) gene expression and secretion in GT1-7 GnRH neurons: signal transduction mechanisms. J Biol Chem 277:251-258
45. Shakil T, Hoque ANE, Husain M, Belsham DD (2002) Differential regulation of gonadotropin-releasing hormone secretion and gene expression by androgen: membrane versus nuclear receptor activation. Mol Endocrinol 16:2592-2602
46. Gillespie JM, Chan BP, Roy D, Cai F, Belsham DD (2003) Expression of circadian rhythm genes in GnRH-secreting GT1-7 neurons. Endocrinology 144:5285-5292
47. Chappell PE, White RS, Mellon PL (2003) Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line. J Neurosci 23:11202-11213
48. Rave-Harel N, Givens ML, Nelson SB, Duong HA, Coss D, Clark ME, Hall SB, Kamps MP, Mellon PL (2004) TALE homeodomain proteins regulate gonadotropin-releasing hormone gene expression independently and via interactions with Oct-1. J Biol Chem 279:30287-30297
49. Rave-Harel N, Miller NL, Givens ML, Mellon PL (2005) The Groucho-related gene family regulates the gonadotropin-releasing hormone gene through interaction with the homeodomain proteins MSX1 and OCT1. J Biol Chem 280:30975-30983
50. Tang Q, Mazur M, Mellon PL (2005) The protein kinase C pathway acts through multiple transcription factors to repress gonadotropin-releasing hormone gene expression in hypothalamic GT1-7 neuronal cells. Mol Endocrinol 19:2769-2779
51. Givens ML, Rave-Harel N, Goonewardena VD, Kurotani R, Berdy SE, Swan CH, Rubenstein JL, Robert B, Mellon PL (2005) Developmental regulation of gonadotropin-releasing hormone gene expression by the MSX and DLX homeodomain protein families. J Biol Chem 280:19156-19165
52. Allen MP, Zeng C, Schneider K, Xiong X, Meintzer MK, Bellosta P, Basilico C, Varnum B, Heidenreich KA, Wierman ME (1999) Growth arrest-specific gene 6 (Gas6)/adhesion related kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt. Mol Endocrinol 13:191-201
53. Wierman ME, Pawlowski JE, Allen MP, Xu M, Linseman DA, Nielson-Priess S (2004) Molecular mechanisms of gonadotropin-releasing hormone neuronal migration. Trends Endocrinol Metab 15:96-102
54. Clark ME, Lawson MA, Belsham DD, Eraly SA, Mellon PL (1997) Molecular aspects of GnRH gene expression. JAI Press, Greenwich, CT
55. Gore AC, Roberts JL (1997) Regulation of gonadotropin-releasing hormone gene expression in vivo and in vitro. Front Neuroendocrinol 18:209-245
56. Belsham DD, Lovejoy DA (2005) Gonadotropin-releasing hormone: gene evolution, expression, and regulation. Vitam Horm 71:59-94
57. Belsham DD, Cai F, Cui H, Smukler SR, Salapatek AM, Shkreta L (2004) Generation of a phenotypic array of hypothalamic neuronal cell models to study complex neuroendocrine disorders. Endocrinology 145:393-400
58. Sawchenko PE, Imaki T, Vale W (1992) Co-localization of neuroactive substances in the endocrine hypothalamus. Ciba Found Symp 168:16-30
59. Broberger C, De Lecea L, Sutcliffe JG, Hokfelt T (1998) Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. J Comp Neurol 402:460-474
60. Hahn TM, Breininger JF, Baskin DG, Schwartz MW (1998) Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1:271-272
61. Bjorbaek C, El-Haschimi K, Frantz JD, Flier JS (1999) The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem 274:30059-30065
62. Bai F, Rankinen T, Charbonneau C, Belsham DD, Rao DC, Bouchard C, Argyropoulos G (2004) Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium. J Med Genet 41:350-353
63. Cui H, Cai F, Belsham DD (2005) Anorexigenic hormones leptin, insulin, and a-melanocyte stimulating hormone directly induce neurotensin (NT) gene expression in novel NT-expressing cell models. J Neurosci 25:9497-9506
64. Wang L, Rotzinger S, Al Chawaf A, Elias CF, Barsyte-Lovejoy D, Qian X, Wang NC, De Cristofaro A, Belsham D, Bittencourt JC, Vaccarino F, Lovejoy DA (2005) Teneurin proteins possess a carboxy terminal sequence with neuromodulatory activity. Brain Res Mol Brain Res 133:253-265
65. Titolo D, Cai F, Belsham DD (2006) Coordinate regulation of neuropeptide Y and agouti-related peptide gene expression by estrogen depends on the ratio of estrogen receptor (ER) alpha to ERbeta in clonal hypothalamic neurons. Mol Endocrinol 20:2080-2092
66. Cui H, Cai F, Belsham DD (2006) Leptin signaling in neurotensin neurons involves STAT, MAP kinases ERK1/2 and p38, through c-Fos and ATF1. FASEB J 20:2654-2656
67. Ning K, Miller LC, Laidlaw HA, Burgess LA, Perera NM, Downes CP, Leslie NR, Ashford ML (2006) A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic beta-cells. EMBO J 25:2377-2387
68. Sagrillo CA, Grattan DR, McCarthy MM, Selmanoff M (1996) Hormonal and neurotransmitter regulation of GnRH gene expression and related reproductive behaviors. Behav Genet 26:241-277
69. Schwanzel-Fukuda M, Jorgenson KL, Bergen HT, Weesner GD, Pfaff DW (1992) Biology of normal luteinizing hormone-releasing hormone neurons during and after their migration from olfactory placode. Endocr Rev 13:623-634
70. Caraty A, Locatelli A, Martin GB (1989) Biphasic response in the secretion of gonadotropin-releasing hormone in ovariectomized ewes injected with oestradiol. J Endocrinol 123:375-382
71. Skynner M, Sim J, Herbison A (1999) Detection of estrogen receptor a and b messenger ribonucleic acids in adult gonadotropin-releasing hormone neurons. Endocrinology 140:5195-5201
72. Butler J, Sjoberg M, Coen C (1999) Evidence for oestrogen receptor alpha-immunoreactivity in gonadotrophin-releasing hormone-expressing neurones. J Neuroendocrinol 11:331-335
73. Hrabovszky E, Shughrue P, Merchenthaler I, Hajszán T, Carpenter C, Liposits Z, Petersen S (2000) Detection of estrogen receptor-b messenger RNA and 125I-estrogen binding sites in LHR-releasing hormone neurons of the rat brain. Endocrinology 141:3506-3509
74. Wierman ME, Kepa JK, Sun W, Gordon DF, Wood WM (1992) Estrogen negatively regulates rat gonadotropin releasing hormone (rGnRH) promoter activity in transfected placental cells. Mol Cell Endocrinol 86:1-10
75. Radovick S, Wray S, Muglia L, Westphal H, Olsen B, Smith E, Patriquin E, Wondisford FE (1994) Steroid hormone regulation and tissue-specific expression of the human GnRH gene in cell culture and transgenic animals. Horm Behav 28:520-529
76. Bowe J, Li XF, Sugden D, Katzenellenbogen JA, Katzenellenbogen BS, O'Byrne KT (2003) The effects of the phytoestrogen, coumestrol, on gonadotropin-releasing hormone (GnRH) mRNA expression in GT1-7 GnRH neurones. J Neuroendocrinol 15:105-108
77. Dorling AA, Todman MG, Korach KS, Herbison AE (2003) Critical role for estrogen receptor alpha in negative feedback regulation of gonadotropin- releasing hormone mRNA expression in the female mouse. Neuroendocrinology 78:204-209
78. Ordog T, Goldsmith JR, ChenMD, ConnaughtonMA, Hotchkiss J, Knobil E (1998) On the mechanism of the positive feedback action of estradiol on luteinizing hormone secretion in the rhesus monkey. J Clin Endocrinol Metab 83:4047-4053
79. Herbison AE (1998) Multimodal influence of estrogen upon gonadotropin-releasing hormone neurons. Endocr Rev 19:302-330
80. Kalra SP (1993) Mandatory neuropeptide-steroid signaling for the preovulatory luteinizing hormone-releasing hormone discharge. Endocr Rev 14:507-538
81. Smith MJ, Jennes L (2001) Neural signals that regulate GnRH neurones directly during the oestrous cycle. Reproduction 122:1-10
82. Wahlestedt C, Heilig M (1994) Neuropeptide Y and related peptides. In: Bloom F (ed) Psychopharmacology - the fourth generation of progress, on-line edition. Lippincott, Williams & Wilkins, Philadelphia, PA
83. Stanley BG, Kyrkouli S, Lampert S, Leibowitz S (1986) Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7:1189-1192
84. Sahu A, Crowley WR, Kalra SP (1995) Evidence that hypothalamic neuropeptide Y gene expression increases before the onset of the preovulatory LH surge. J Neuroendocrinol 7:291-296
85. Kalra PS, Bonavera JJ, Kalra SP (1995) Central administration of antisense oligodeoxynucleotides to neuropeptide Y (NPY) mRNA reveals the critical role of newly synthesized NPY in regulation of LHRH release. Regulatory Pept 59:215-220
86. Kalra PS, Kalra SP (2000) Use of antisense oligodeoxynucleotides to study the physiological functions of neuropeptide Y. Methods 22:249-254
87. Kasuya E, Mizuno M, Watanabe G, Terasawa E (1998) Effects of an antisense oligodeoxynucleotide for neuropeptide Y mRNA on in vivo luteinizing hormone-releasing hormone release in ovariectomized female rhesus monkeys. Regulatory Pept 75-76:319-325
88. Xu M, Hill JW, Levine JE (2000) Attenuation of luteinizing hormone surges in neuropeptide Y knockout mice. Neuroendocrinology 72:263-271
89. Li C, Chen P, Smith MS (1999) Morphological evidence for direct interaction between arcuate nucleus neuropeptide Y (NPY) neurons and gonadotropin-releasing hormone neurons and the possible involvement of NPY Y1 receptors. Endocrinology 140:5382-5390
90. Dudas B, Mihaly A, Merchenthaler I (2000) Topography and associations of luteinizing hormone-releasing hormone and neuropeptide Y-immunoreactive neuronal systems in the human diencephalon. J Comp Neurol 427:593-603
91. Simonian SX, Herbison AE (1997) Differential expression of estrogen receptor and neuropeptide Y by brainstem A1 and A2 noradrenaline neurons. Neuroscience 76:517-529
92. Ahima RS, Osei SY (2001) Molecular regulation of eating behavior: new insights and prospects for therapeutic strategies. Trends Mol Med 7:205-213
93. Spiegelman BM, Flier JS (2001) Obesity and the regulation of energy balance. Cell 104:531-543
94. Palmiter RD, Erickson JC, Hollopeter G, Baraban SC, Schwartz MW (1998) Life without neuropeptide Y. Recent Prog Horm Res 53:163-199
95. Morton GJ, Schwartz MW (2001) The NPY/AgRP neuron and energy homeostasis. Int J Obes Relat Metab Disord 25:S56-S62
96. Cone RD (1999) The central melanocortin system and energy homeostasis. Trends Endocrinol Metab 10:211-216
97. Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396:670-674
98. Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni R, Kokkotou E, Elmquist J, Lowell B, Flier JS, Maratos-Flier E (2001) Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107:379-386
99. Tritos NA, Maratos-Flier E (1999) Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone. Neuropeptides 33:339-349
100. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131-141
101. Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD (1999) Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 24:155-163
102. Sahu A (1998) Evidence suggesting that galanin (GAL), melanin-concentrating hormone (MCH), neurotensin (NT), proopiomelanocortin (POMC) and neuropeptide Y (NPY) are targets of leptin signaling in the hypothalamus. Endocrinology 139:795-798
103. Ahima RS, Flier JS (2000) Leptin. Annu Rev Physiol 62:413-437
104. Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B (1998) Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 18:559-572
105. Baskin DG, Hahn TM, Schwartz MW (1999) Leptin sensitive neurons in the hypothalamus. Horm Metab Res 31:345-350
106. Iqbal J, Pompolo S, Murakami T, Grouzmann E, Sakurai T, Meister B, Clarke IJ (2001) Immunohistochemical characterization of localization of long-form leptin receptor (OB-Rb) in neurochemically defined cells in the ovine hypothalamus. Brain Res 920:55-64
107. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, Banks AS, Lavery HJ, Haq AK, Maratos-Flier E, Neel BG, Schwartz MW, Myers MG (2003) STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421:856-859
108. Kim MS, Pak YK, Jang PG, Namkoong C, Choi YS, Won JC, Kim KS, Kim SW, Kim HS, Park JY, Kim YB, Lee KU (2006) Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nat Neurosci 9:901-906
109. Zhang EE, Chapeau E, Hagihara K, Feng GS (2004) Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc Natl Acad Sci U S A 101:16064-16069
110. Cohen P, Zhao C, Cai X, Montez JM, Rohani SC, Feinstein P, Mombaerts P, Friedman JM (2001) Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 108:1113-1121
111. de Luca C, Kowalski TJ, Zhang Y, Elmquist JK, Lee C, Kilimann MW, Ludwig T, Liu SM, Chua SC Jr (2005) Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest 115:3484-3493
112. Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS, Bjorbaek C, Flier JS, Saper CB, Elmquist JK (1999) Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23:775-786
113. Watanobe H, Habu S (2002) Leptin regulates growth hormone-releasing factor, somatostatin, and alpha-melanocyte-stimulating hormone but not neuropeptide Y release in rat hypothalamus in vivo: relation with growth hormone secretion. J Neurosci 22:6265-6271
114. Sahu A, Carraway RE, Wang YP (2001) Evidence that neurotensin mediates the central effect of leptin on food intake in rat. Brain Res 888:343-347
115. Richy S, Burlet A, Max J, Burlet C, Beck B (2000) Effect of chronic intraperitoneal injections of leptin on hypothalamic neurotensin content and food intake. Brain Res 862:276-279
116. Carraway R, Leeman SE (1973) The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem 248:6854-6861
117. Carraway R, Leeman SE (1975) The amino acid sequence of a hypothalamic peptide, neurotensin. J Biol Chem 250:1907-1911
118. Remaury A, Vita N, Gendreau S, Jung M, Arnone M, Poncelet M, Culouscou JM, Le Fur G, Soubrie P, Caput D, Shire D, Kopf M, Ferrara P (2002) Targeted inactivation of the neurotensin type 1 receptor reveals its role in body temperature control and feeding behavior but not in analgesia. Brain Res 953:63-72
119. Meyer-Spasche A, Reed HE, Piggins HD (2002) Neurotensin phase-shifts the firing rate rhythm of neurons in the rat suprachiasmatic nuclei in vitro. Eur J Neurosci 16:339-344
120. Dobner PR, Fadel J, Deitemeyer N, Carraway RE, Deutch AY (2001) Neurotensin-deficient mice show altered responses to antipsychotic drugs. Proc Natl Acad Sci U S A 98:8048-8053
121. Rostene WH, Alexander MJ (1997) Neurotensin and neuroendocrine regulation. Front Neuroendocrinol 18:115-173
122. Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, Elmquist JK, Flier JS, Hollenberg AN (2001) Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J Clin Invest 107: 111-120
123. Elias CF, Kelly JF, Lee CE, Ahima RS, Drucker DJ, Saper CB, Elmquist JK (2000) Chemical characterization of leptin-activated neurons in the rat brain. J Comp Neurol 423:261-281
124. Beck B, Stricker-Krongrad A, Richy S, Burlet C (1998) Evidence that hypothalamic neurotensin signals leptin effects on feeding behavior in normal and fat-preferring rats. Biochem Biophys Res Commun 252:634-638
125. Wilding JP, Gilbey SG, Bailey CJ, Batt RA, Williams G, Ghatei MA, Bloom SR (1993) Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 132:1939-1944
126. Stanley BG, Hoebel BG, Leibowitz SF (1983) Neurotensin: effects of hypothalamic and intravenous injections on eating and drinking in rats. Peptides 4:493-500
127. Harrison RJ, McNeil GP, Dobner PR (1995) Synergistic activation of neurotensin/neuromedin N gene expression by c-Jun and glucocorticoids: novel effects of Fos family proteins. Mol Endocrinol 9:981-993
128. Watters JJ, Dorsa DM (1998) Transcriptional effects of estrogen on neuronal neurotensin gene expression involve cAMP/protein kinase A-dependent signaling mechanisms. J Neurosci 18:6672-6680
129. Kaszubska W, Falls HD, Schaefer VG, Haasch D, Frost L, Hessler P, Kroeger PE, White DW, Jirousek MR, Trevillyan JM (2002). Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line. Mol Cell Endocrinol 195:109-118