Abstract

Neuropeptide Y (NPY) has been recently characterized in the goldfish and the sequence deduced from goldfish brain cDNA clones reveals that goldfish NPY (gNPY) has over 86% identity with human NPY (hNPY) (Blomqvist et al., 1992, Proc. Natl. Acad. Sci. USA 89, 2350-2354). In the present study, we used synthetic gNPY to investigate the role of NPY in the regulation of growth hormone (GH) and gonadotropin-II (GtH-II) in the goldfish. The dose-response relationships of gNPY on GH and GtH-II release were first tested using an in vitro perifusion system for pituitary fragments. It was found that gNPY stimulated both GH and GtH-II release in a dose-dependent manner, with ED 50 values of 1.89 ± 0.9 n M for GH and 4.19 ± 2.9 n M for GtH-II. In addition, the C-terminal fragment gNPY (18-36) stimulated the release of both GH and GtH-II, but with lower potency than did the intact molecule. These results confirm our previous findings using hNPY. The interactions of gNPY and other GH and GtH-II regulators were also examined in the present studies. Prolonged infusion of sGnRH induced initial peak releases of GH and GtH-II, followed by a second phase of sustained hormone release at a reduced level. Application of a 5-min pulse of gNPY during the second phase of sGnRH action further stimulated GH and GtH-II release, but only to the levels similar to those induced by gNPY alone. Prolonged infusion with gNPY induced a rapid desensitization of GH and GtH-II release; the hormone levels returned to basal within 25 min in the continued presence of gNPY. Administration of 5-min pulse of sGnRH during the desensitization phase of continuous gNPY perifusion induced a similar GH response to that induced by sGnRH alone, whereas the GtH-II responses to sGnRH given during gNPY infusion were smaller than the responses to sGnRH alone, suggesting that the mechanisms of gNPY stimulation on GH and GtH-II release may be somewhat different. The gNPY-induced GH release was blocked by somatostatin, a known GH inhibitor; the gNPY-induced GtH-II release was reduced by dopamine, a known inhibitor for GtH-II. Finally, intraperitoneal injection of gNPY induced time- and dose-dependent increases in serum GH and GtH-II levels. Together, these results suggest that NPY may play a physiological role in the regulation of GH and GtH-II secretion in the goldfish.

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