HYPOTHALAMIC NEUROPEPTIDE-Y, ITS GENE-EXPRESSION AND RECEPTOR ACTIVITY - RELATION TO CIRCULATING CORTICOSTERONE IN ADRENALECTOMIZED RATS

Previous evidence has suggested a possible relationship between the ad renal steroid, corticosterone (CORT) and neuropeptide Y (NPY) in the b rain. To provide a more systematic analysis of this interaction, the p resent study employed a variety of techniques, including in situ hybri dization to measure NPY gene expression, radioimmunoassay to examine p eptide levels and radioligand [I-125]peptide YY (PYY) binding for anal ysis of peptide receptors. The results show that adrenalectomy (ADX), which caused a decline in CORT to levels < 0.3 mu g%, has generally li ttle impact on the hypothalamic NPY projection system under normal, ba sal conditions. This includes peptide gene expression or content in th e area of its cell bodies (arcuate nucleus, ARC), in addition to pepti de binding at its receptor sites. While it also includes peptide conte nt at most hypothalamic terminal sites, there are three notable except ions, namely, the medial paraventricular (PVN) and dorsomedial nuclei and medial preoptic area, where NPY nerve terminals and glucocorticoid receptors are particularly dense and the decline in CORT through ADX markedly reduces NPY content. In contrast, evidence obtained from CORT replacement in ADX rats shows that this steroid has profound impact o n all components of the hypothalamic NPY system. This peptide-steroid interaction is apparent at the level of the cell body (ARC), as well a s at the nerve terminal or receptor site (PVN and ARC), where CORT lev els > 10 mu g% strongly potentiate NPY gene expression, peptide conten t and radioligand binding. These and other findings suggest that this CORT-NPY interaction in the hypothalamus occurs physiologically under conditions, e.g., at the onset of the active feeding cycle, when circu lating CORT normally rises.