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Elevated Corticosterone Is Not Required for the Rapid Induction of Neuropeptide Y Gene Expression by an Overnight Fast¹

Department of Physiology (E.S.H., M.F.D.), University of California, San Francisco, California 94143-0444; and Genentech, Inc. (N.L.), South San Francisco, California 94080

Address all correspondence and requests for reprints to: E. Simon Hanson, Department of Physiology, University of California, San Francisco, San Francisco, California 94143-0444. E-mail: hanson{at}itsa.ucsf.edu

Fasting stimulates corticosterone (B) secretion and the expression and secretion of hypothalamic neuropeptide Y in rats. These studies tested the hypothesis that the rapid and marked fasting-induced increases in plasma B are responsible for stimulation of neuropeptide Y (NPY) gene expression. Plasma leptin and insulin were measured because they are also signals known to affect NPY messenger RNA (mRNA). Intact or adrenalectomized rats given a low fixed level of corticosterone (B replaced) were fasted for 48 h. NPY mRNA in the mediobasal hypothalamus, measured by nuclease protection assay, was elevated similarly above ad lib-fed controls in both intact and B replaced groups at 15 and 48 h after the onset of fasting. NPY immunoreactivity in the mediobasal hypothalamus increased between 3 and 48 h after onset of the fast in intact but not in B replaced groups. The fasting-induced decreases in leptin observed in intact rats at 48 h did not occur in B replaced rats. Fasting-induced decreases in insulin occurred in B replaced rats but not in intact rats. We conclude that: 1) elevated B is not required for fasting-induced increases in hypothalamic NPY gene expression; and 2) decreases in neither leptin nor insulin alone signal the changes that occur in NPY mRNA in fasted rats.

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