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Am J Physiol Endocrinol Metab 293: E1265-E1273, 2007. First published August 28, 2007; doi:10.1152/ajpendo.00425.2007
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Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod

Eva Vigo, Juan Roa, Rafael Pineda, Juan M. Castellano, Victor M. Navarro, Enrique Aguilar, Leonor Pinilla, and Manuel Tena-Sempere

Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University of Córdoba, Cordoba; and CIBER (CB06/03) Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain

Submitted 4 July 2007 ; accepted in final form 23 August 2007

Neuromedin U (NMU) is a widely spread neuropeptide, with predominant expression at the gastrointestinal tract and brain, putatively involved in the regulation of a diversity of biological functions, including food intake, energy balance and circadian rhythms; all closely related to reproduction. Yet, the implication of NMU in the control of the gonadotropic axis remains scarcely studied. We report herein analyses on the hypothalamic expression and function of NMU in different physiological and experimental states of the rat reproductive system. Expression of NMU mRNA at the hypothalamus was persistently detected along female postnatal development, with maximum levels in adulthood that fluctuated across the cycle and were modulated by ovarian steroids. Acute central administration of NMU evoked increases of serum LH levels in pubertal female rats, while repeated injection of NMU tended to advance vaginal opening. Likewise, central injection of NMU increased serum LH concentrations in cycling female rats, with peak responses in estrus. In contrast, NMU significantly inhibited preelevated LH secretion in gonadectomized and kisspeptin-treated rats. Finally, in noncycling females due to photoperiodic manipulation (constant light), hypothalamic NMU mRNA levels were markedly depressed, but relative LH responses to exogenous NMU were significantly augmented. All together, our present data support a predominant stimulatory role of NMU in the control of the female gonadotropic axis, which appears under the influence of developmental, hormonal, and photoperiodic cues, and might contribute to the joint regulation of energy balance, biological rhythms, and reproduction.

neuromedin S; luteinizing hormone; estrous cycle; estrogen; progesterone; puberty; photoperiod; suprachiasmatic nucleus; rat


Address for reprint requests and other correspondence: M. Tena-Sempere, Physiology Section, Dept. of Cell Biology, Physiology and Immunology. Faculty of Medicine, Univ. of Córdoba, Avda. Menéndez Pidal s/n, 14004 Cordoba, Spain (e-mail: fi1tesem{at}uco.es)






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