Functional heterogeneity in neuropeptide-Y-producing cells in the rat brain as revealed by testosterone action

Abstract

Despite the widespread distribution of neuropeptide-Y (NPY) in various hypothalamic sites, castration reduced and testosterone (T) replacement restored NPY levels selectively in the median eminence (ME), arcuate nucleus (ARC), and ventromedial nucleus (VMN). Since androgen-concentrating cells and NPY-producing cells display overlapping distribution in the ARC and brain stem (BS), we assessed the participation of BS NPY cells in the steroid-dependent site-specific effects on NPY levels. The BS projections to the hypothalamus were severed by bilateral neural transection (BNT) with a knife lowered on either side of the sagittal sinus to the depth of the dorsal tegmentum in the mesencephalon in intact, castrated, or castrated rats that additionally received sc T implants to maintain physiological T levels. Two weeks later, NPY concentrations in microdissected hypothalamic sites and serum LH and T levels were quantitated by RIA. Castration decreased and T replacement increased NPY concentrations in only three sites, such as the VMN, ARC, and ME. In response to BNT in gonadally intact rats, a different site-specific response of NPY levels was observed; NPY levels decreased in the ME, as seen after castration, and, additionally, decreased in the medial preoptic area, paraventricular nucleus, and dorsomedial nucleus, suggesting that BS NPY neurons innervate these four sites. When castration and BNT were performed simultaneously, a combined regional response was evident. NPY levels decreased in six sites, including two sites (ARC and VMN) that normally respond to castration alone, three sites (medial preoptic area, paraventricular nucleus, and dorsomedial nucleus) that normally respond to BNT alone, and the ME, the only site that showed reduction of NPY levels of similar magnitude after either castration or BNT, but the response of combined surgery was not additive. This observation suggested that gonadal steroids act outside the hypothalamus to raise ME NPY levels, and therefore, BNT in intact rats impaired the effectiveness of steroids. To test this hypothesis, the effects of physiological T replacement in the castrate plus BNT group were studied. We observed that whereas T replacement readily raised NPY levels in the VMN and ARC, it was completely ineffective in the third T-dependent site, the ME. Collectively, these findings revealed a functional heterogeneity among NPY-producing cells in response to T. Apparently, there are two distinct neural sites in the rat brain where T acts to exert a site-specific stimulatory effect on NPY in the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)