title: Hindbrain catecholamine neurons modulate the growth hormone but not the feeding response to ghrelin.
abstract: The gastrointestinal peptide, ghrelin, elicits feeding and secretion when administered systemically or centrally. Previous studies have suggested that hypothalamic projections of hindbrain catecholamine neurons are involved in both of these actions of ghrelin. The purpose of this study was to further assess the role of hindbrain catecholamine neurons in ghrelin-induced feeding and GH secretion and to determine the anatomical distribution of the catecholamine neurons involved. We lesioned noradrenergic and adrenergic neurons that innervate the medial hypothalamus by microinjecting the retrogradely transported immunotoxin, saporin (SAP) conjugated to antidopamine-beta-hydroxylase (DSAP) into the paraventricular nucleus of the hypothalamus. Controls were injected with unconjugated SAP. We found that the DSAP lesion did not impair the feeding response to central or peripheral ghrelin administration, indicating that these neurons are not required for ghrelin's orexigenic effect. However, the GH response to ghrelin was prolonged significantly in DSAP-lesioned rats. We also found that expression of Fos, an indicator of neuronal activation, was significantly enhanced over baseline levels in A1, A1/C1, C1, and A5 cell groups after ghrelin treatment and in A1, A1/C1, and A5 cell groups after GH treatment. The similar pattern of Fos expression in catecholamine cell groups after GH and ghrelin and the prolonged GH secretion in response to ghrelin in DSAP rats together suggest that activation of hindbrain catecholamine neurons by ghrelin or GH could be a component of a negative feedback response controlling GH levels.
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, WA 99164-6520, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Emanuel
authors.forename: Sue
authors.initials: S
authors.lastname: Ritter
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D054439:Ghrelin / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000166:cytology* / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry / Q000494:pharmacology; D000076985:Saporins
chemical_list: D002395:Catecholamines; D054439:Ghrelin; D054789:Ribosome Inactivating Proteins, Type 1; D013006:Growth Hormone; D000076985:Saporins
references.citation: Biochem Biophys Res Commun. 2000 Aug 28;275(2):477-80
references.pmid: 10964690
references.citation: Peptides. 2003 Jun;24(6):919-23
references.pmid: 12948845
references.citation: Science. 1996 Aug 16;273(5277):974-7
references.pmid: 8688086
references.citation: Brain Res. 2008 Jul 7;1218:151-7
references.pmid: 18514175
references.citation: Brain Res. 1994 Mar 28;641(1):111-20
references.pmid: 8019836
references.citation: Endocrinology. 2000 Nov;141(11):4255-61
references.pmid: 11089560
references.citation: Physiol Rev. 2005 Apr;85(2):495-522
references.pmid: 15788704
references.citation: J Clin Endocrinol Metab. 2005 Aug;90(8):4521-4
references.pmid: 15914532
references.citation: Diabetes. 2001 Nov;50(11):2540-7
references.pmid: 11679432
references.citation: Nature. 2001 Jan 11;409(6817):194-8
references.pmid: 11196643
references.citation: Diabetes. 2001 Nov;50(11):2438-43
references.pmid: 11679419
references.citation: Cell Metab. 2006 Oct;4(4):323-31
references.pmid: 17011505
references.citation: J Clin Endocrinol Metab. 2001 Dec;86(12):5992
references.pmid: 11739476
references.citation: Neuroscience. 1995 Jan;64(2):477-505
references.pmid: 7700534
references.citation: Physiol Behav. 2007 Apr 23;90(5):744-50
references.pmid: 17289093
references.citation: Nature. 1999 Dec 9;402(6762):656-60
references.pmid: 10604470
references.citation: Neuron. 2003 Feb 20;37(4):649-61
references.pmid: 12597862
references.citation: Neuroendocrinology. 1993 May;57(5):921-7
references.pmid: 8105398
references.citation: J Neuroendocrinol. 1993 Apr;5(2):145-50
references.pmid: 8097943
references.citation: Endocrinology. 2005 Aug;146(8):3518-25
references.pmid: 15890776
references.citation: Brain Res. 1982 Nov;257(3):275-325
references.pmid: 6756545
references.citation: Biochem Biophys Res Commun. 2001 Mar;281(5):1220-5
references.pmid: 11243865
references.citation: Physiol Behav. 2004 Jul;81(5):719-33
references.pmid: 15234177
references.citation: J Clin Invest. 2009 Nov;119(11):3189-202
references.pmid: 19884662
references.citation: Neuroendocrinology. 1996 Aug;64(2):131-8
references.pmid: 8857607
references.citation: Prog Brain Res. 1983;60:19-29
references.pmid: 6198687
references.citation: Eur J Endocrinol. 2004 Oct;151(4):447-50
references.pmid: 15476443
references.citation: Peptides. 2005 Nov;26(11):2274-9
references.pmid: 16137788
references.citation: Neuroreport. 2004 Jun 7;15(8):1365-7
references.pmid: 15167567
references.citation: J Nutr. 2005 May;135(5):1320-5
references.pmid: 15867333
references.citation: Neuroendocrinology. 1993 Apr;57(4):687-92
references.pmid: 8396221
references.citation: Brain Res. 1998 Sep 14;805(1-2):41-54
references.pmid: 9733914
references.citation: Endocrinology. 2003 Mar;144(3):967-74
references.pmid: 12586774
references.citation: Vitam Horm. 2008;77:47-88
references.pmid: 17983853
references.citation: Endocrinology. 2005 Mar;146(3):1179-91
references.pmid: 15604214
references.citation: Curr Neuropharmacol. 2009 Mar;7(1):37-49
references.pmid: 19721816
references.citation: Gastroenterology. 2002 Oct;123(4):1120-8
references.pmid: 12360474
references.citation: Ann N Y Acad Sci. 2009 Apr;1163:137-53
references.pmid: 19456335
references.citation: Diabetes. 2003 Sep;52(9):2260-5
references.pmid: 12941764
references.citation: Endocrinology. 2005 Jun;146(6):2510-6
references.pmid: 15774556
references.citation: J Neurosci. 2006 Oct 25;26(43):11052-60
references.pmid: 17065447
references.citation: Brain Res Bull. 1988 Dec;21(6):905-12
references.pmid: 3224284
references.citation: Regul Pept. 2003 Mar 28;111(1-3):161-7
references.pmid: 12609764
references.citation: Endocrinology. 2003 Jan;144(1):75-83
references.pmid: 12488332
references.citation: Regul Pept. 2001 Jun 15;99(2-3):141-50
references.pmid: 11384775
references.citation: J Comp Neurol. 1985 Mar 15;233(3):308-32
references.pmid: 2858497
references.citation: Circulation. 2001 Oct 23;104(17):2034-8
references.pmid: 11673342
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1350-8
references.pmid: 16469825
references.citation: Neuroendocrinology. 1994 Jan;59(1):29-34
references.pmid: 7908421
references.citation: J Neurosci. 2009 Jan 7;29(1):280-7
references.pmid: 19129404
references.citation: J Comp Neurol. 2001 Apr 2;432(2):197-216
references.pmid: 11241386
references.citation: Gut. 2003 Jul;52(7):947-52
references.pmid: 12801949
references.citation: Endocrinology. 2003 Apr;144(4):1357-67
references.pmid: 12639919
references.citation: Neurosci Biobehav Rev. 1988 Summer;12(2):101-9
references.pmid: 2845312
references.citation: Peptides. 2007 Feb;28(2):214-25
references.pmid: 17194499