Hypothalamic Ghrelin Treatment Modulates NPY-but Not CRH-ergic Activity in Adrenalectomized Rats Subjected to Food Restriction: Evidence of a Novel Hypothalamic Ghrelin Effect

Abstract

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.