Hypothalamic ghrelin treatment modulates NPY-but not CRH-ergic activity in adrenalectomized rats subjected to food restriction: Evidence of a novel hypothalamic ghrelin effect

It has been proposed that ghrelin induces food intake by a mechanism due to the stimulation of hypothalamic NPY-ergic activity. It is recognized that bilateral adrenalectomy (ADX) enhances hypothalamic CRH-ergic function and reduces appetite. Thus, the aim of the present study was to test whether, i...

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Veröffentlicht in:Endocrine 2006-06, Vol.29 (3), p.477-484
Hauptverfasser: Spinedi, Eduardo, Voirol, Marie-Jeanne, Verdumo, Chantal, Giacominni, Marco, Pralong, François, Gaillard, Rolf C
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container_issue 3
container_start_page 477
container_title Endocrine
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creator Spinedi, Eduardo
Voirol, Marie-Jeanne
Verdumo, Chantal
Giacominni, Marco
Pralong, François
Gaillard, Rolf C
description It has been proposed that ghrelin induces food intake by a mechanism due to the stimulation of hypothalamic NPY-ergic activity. It is recognized that bilateral adrenalectomy (ADX) enhances hypothalamic CRH-ergic function and reduces appetite. Thus, the aim of the present study was to test whether, icv-administered, ghrelin modulates NPY- and CRH-ergic functions after food restriction (FR) and glucocorticoid deprivation. For this purpose, 1 microg ghrelin was administered icv to ad libitum (AL) eating and to corticosterone (B)-depleted (ADX) and -replete (sham and ADX+B) male animals habituated, for 15 d, to FR. Food intake, hypothalamic function, and peripheral ghrelin, ACTH, and B concentrations were evaluated 2 h after ghrelin administration. Results indicate that while icv ghrelin treatment stimulated 2-h food intake in AL rats, it failed to do so in sham- and ADX+B-FR animals; moreover, 2-h food intake was inhibited by icv ghrelin treatment in ADX-FR rats. Regarding peripheral hormone levels: (a) basal circulating ghrelin levels, already enhanced (vs AL rats) by FR, significantly increased 2 h after icv ghrelin treatment in AL and sham-FR rats; (b) central ghrelin treatment stimulated ACTH secretion in circulation of AL and glucocorticoid-replete-FR rats; and (c) B circulating levels remained unchanged after ghrelin treatment, although they were in relation to the food intake condition of rats. Finally, hypothalamic NPY mRNA expression was enhanced by FR and, in response to icv ghrelin treatment, it decreased in ADX-FR rats only. ADX-enhanced hypothalamic CRH mRNA levels were reduced by ghrelin icv administration only when animals received B replacement therapy. Our data indicate an inhibitory effect of hypothalamic ghrelin on NPY-ergic activity in FR rats lacking endogenous glucocorticoid.
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It is recognized that bilateral adrenalectomy (ADX) enhances hypothalamic CRH-ergic function and reduces appetite. Thus, the aim of the present study was to test whether, icv-administered, ghrelin modulates NPY- and CRH-ergic functions after food restriction (FR) and glucocorticoid deprivation. For this purpose, 1 microg ghrelin was administered icv to ad libitum (AL) eating and to corticosterone (B)-depleted (ADX) and -replete (sham and ADX+B) male animals habituated, for 15 d, to FR. Food intake, hypothalamic function, and peripheral ghrelin, ACTH, and B concentrations were evaluated 2 h after ghrelin administration. Results indicate that while icv ghrelin treatment stimulated 2-h food intake in AL rats, it failed to do so in sham- and ADX+B-FR animals; moreover, 2-h food intake was inhibited by icv ghrelin treatment in ADX-FR rats. Regarding peripheral hormone levels: (a) basal circulating ghrelin levels, already enhanced (vs AL rats) by FR, significantly increased 2 h after icv ghrelin treatment in AL and sham-FR rats; (b) central ghrelin treatment stimulated ACTH secretion in circulation of AL and glucocorticoid-replete-FR rats; and (c) B circulating levels remained unchanged after ghrelin treatment, although they were in relation to the food intake condition of rats. Finally, hypothalamic NPY mRNA expression was enhanced by FR and, in response to icv ghrelin treatment, it decreased in ADX-FR rats only. ADX-enhanced hypothalamic CRH mRNA levels were reduced by ghrelin icv administration only when animals received B replacement therapy. 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Regarding peripheral hormone levels: (a) basal circulating ghrelin levels, already enhanced (vs AL rats) by FR, significantly increased 2 h after icv ghrelin treatment in AL and sham-FR rats; (b) central ghrelin treatment stimulated ACTH secretion in circulation of AL and glucocorticoid-replete-FR rats; and (c) B circulating levels remained unchanged after ghrelin treatment, although they were in relation to the food intake condition of rats. Finally, hypothalamic NPY mRNA expression was enhanced by FR and, in response to icv ghrelin treatment, it decreased in ADX-FR rats only. ADX-enhanced hypothalamic CRH mRNA levels were reduced by ghrelin icv administration only when animals received B replacement therapy. 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Voirol, Marie-Jeanne ; Verdumo, Chantal ; Giacominni, Marco ; Pralong, François ; Gaillard, Rolf C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-6a0f2e8d7726590604dfa3854f60747d2c68ba05a64fa0d2ab7975392aeb51b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adrenalectomy</topic><topic>Adrenocorticotropic Hormone - blood</topic><topic>Animals</topic><topic>Body Weight</topic><topic>Corticotropin-Releasing Hormone - metabolism</topic><topic>Drug Administration Routes</topic><topic>Eating - drug effects</topic><topic>Food Deprivation - physiology</topic><topic>Gene Expression - drug effects</topic><topic>Ghrelin</topic><topic>Glucocorticoids - physiology</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - metabolism</topic><topic>Injections - methods</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Neuropeptide Y - metabolism</topic><topic>Peptide Hormones - administration &amp; 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It is recognized that bilateral adrenalectomy (ADX) enhances hypothalamic CRH-ergic function and reduces appetite. Thus, the aim of the present study was to test whether, icv-administered, ghrelin modulates NPY- and CRH-ergic functions after food restriction (FR) and glucocorticoid deprivation. For this purpose, 1 microg ghrelin was administered icv to ad libitum (AL) eating and to corticosterone (B)-depleted (ADX) and -replete (sham and ADX+B) male animals habituated, for 15 d, to FR. Food intake, hypothalamic function, and peripheral ghrelin, ACTH, and B concentrations were evaluated 2 h after ghrelin administration. Results indicate that while icv ghrelin treatment stimulated 2-h food intake in AL rats, it failed to do so in sham- and ADX+B-FR animals; moreover, 2-h food intake was inhibited by icv ghrelin treatment in ADX-FR rats. Regarding peripheral hormone levels: (a) basal circulating ghrelin levels, already enhanced (vs AL rats) by FR, significantly increased 2 h after icv ghrelin treatment in AL and sham-FR rats; (b) central ghrelin treatment stimulated ACTH secretion in circulation of AL and glucocorticoid-replete-FR rats; and (c) B circulating levels remained unchanged after ghrelin treatment, although they were in relation to the food intake condition of rats. Finally, hypothalamic NPY mRNA expression was enhanced by FR and, in response to icv ghrelin treatment, it decreased in ADX-FR rats only. ADX-enhanced hypothalamic CRH mRNA levels were reduced by ghrelin icv administration only when animals received B replacement therapy. Our data indicate an inhibitory effect of hypothalamic ghrelin on NPY-ergic activity in FR rats lacking endogenous glucocorticoid.</abstract><cop>United States</cop><pmid>16943587</pmid><doi>10.1385/ENDO:29:3:477</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adrenalectomy
Adrenocorticotropic Hormone - blood
Animals
Body Weight
Corticotropin-Releasing Hormone - metabolism
Drug Administration Routes
Eating - drug effects
Food Deprivation - physiology
Gene Expression - drug effects
Ghrelin
Glucocorticoids - physiology
Hypothalamus - drug effects
Hypothalamus - metabolism
Injections - methods
Leptin - blood
Male
Neuropeptide Y - metabolism
Peptide Hormones - administration & dosage
Peptide Hormones - blood
Peptide Hormones - pharmacology
Rats
Rats, Wistar
RNA, Messenger - metabolism
title Hypothalamic ghrelin treatment modulates NPY-but not CRH-ergic activity in adrenalectomized rats subjected to food restriction: Evidence of a novel hypothalamic ghrelin effect
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