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Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat

Jethwa, Preeti H.; Smith, Kirsty L.; Small, Caroline J.; Abbott, Caroline R.; Darch, Sarah J.; Murphy, Kevin G.; Seth, Asha; Semjonous, Nina M.; Patel, Sejal R.; Todd, Jeannie F.; Ghatei, Mohammad A.; Bloom, Stephen R.

Authors

Kirsty L. Smith

Caroline J. Small

Caroline R. Abbott

Sarah J. Darch

Kevin G. Murphy

Asha Seth

Nina M. Semjonous

Sejal R. Patel

Jeannie F. Todd

Mohammad A. Ghatei

Stephen R. Bloom



Abstract

Intracerebroventricular (ICV) administration of the hypothalamic neuropeptide neuromedin U (NMU) or the adipostat hormone leptin increases plasma ACTH and corticosterone. The relationship between leptin and NMU in the regulation of the hypothalamo-pituitary adrenal (HPA) axis is currently unknown. In this study, leptin (1 nM) significantly increased the release of CRH from ex vivo hypothalamic explants by 207 ± 8.4% (P < 0.05 vs. basal), an effect blocked by the administration of anti-NMU IgG. The ICV administration of leptin (10 μg, 0.625 nmol) increased plasma ACTH and corticosterone 20 min after injection [plasma ACTH (picograms per milliliter): vehicle, 63 ± 20, leptin, 135 ± 36, P < 0.05; plasma corticosterone (nanograms per milliliter): vehicle, 285 ± 39, leptin, 452 ± 44, P < 0.01]. These effects were partially attenuated by the prior administration of anti-NMU IgG. Peripheral leptin also stimulated ACTH release, an effect attenuated by prior ICV administration of anti-NMU IgG. We examined the diurnal pattern of hypothalamic NMU mRNA expression and peptide content, plasma leptin, and plasma corticosterone. The diurnal changes in hypothalamic NMU mRNA expression were positively correlated with hypothalamic NMU peptide content, plasma corticosterone, and plasma leptin. The ICV administration of anti-NMU IgG significantly attenuated the dark phase rise in corticosterone [corticosterone (nanograms per milliliter): vehicle, 493 ± 38; NMU IgG, 342 ± 47 (P < 0.05)]. These studies suggest that NMU may play a role in the regulation of the HPA axis and partially mediate leptin-induced HPA stimulation. Copyright © 2006 by The Endocrine Society.

Citation

Jethwa, P. H., Smith, K. L., Small, C. J., Abbott, C. R., Darch, S. J., Murphy, K. G., …Bloom, S. R. (2006). Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat. Endocrinology, 147(6), 2886-2892. https://doi.org/10.1210/en.2005-0983

Journal Article Type Article
Acceptance Date Mar 13, 2006
Online Publication Date Jun 1, 2006
Publication Date Jun 1, 2006
Deposit Date Jun 25, 2021
Journal Endocrinology
Print ISSN 0013-7227
Electronic ISSN 1945-7170
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 147
Issue 6
Pages 2886-2892
DOI https://doi.org/10.1210/en.2005-0983
Public URL https://nottingham-repository.worktribe.com/output/3158493
Publisher URL https://academic.oup.com/endo/article/147/6/2886/2879488