Endocrine Abstracts (2006) 11 P683

Neuromedin U (NMU) and Neuromedin S (NMS) function as putative rregulators of the gonadotropic axis in the rat

E Vigo, J Roa, JM Castellano, R Fernandez-Fernandez, VM Navarro, R Pineda, E Aguilar, L Pinilla & M Tena-Sempere

University of Cordoba, Cordoba, Spain.

Neuromedin U (NMU) is a brain-gut peptide originally isolated from porcine spinal cord, and later found in other species. NMU acts through two receptors named NMU1R (abundant in peripheral tissues) and NMU2R (apparently restricted to specific brain regions). Besides its potential implication in the control of stress responses, NMU is abundantly expressed in the ventromedial hypothalamic area and has been involved, as satiety factor, in the regulation of food intake. Very recently, a novel neuropeptide, structurally related to NMU, has been identified in rat brain, and termed neuromedin S (NMS). NMS shares its C-terminal region with NMU and acts through the same receptors. NMS has been reported as potent anorexigenic factor in the hypothalamus, and it may play a role in the regulation of circadian rhythms.

A wealth of data has now demonstrated that a large number of regulators of feeding behaviour (e.g. leptin, ghrelin and orexin) are also implicated in the control of the gonadotropic axis, thereby contributing to the joint regulation of energy balance and reproduction. However, the implication of NMU and NMS in the regulation of gonadotropin secretion remains so far scarcely evaluated. In the present study, we analyzed the effects of NMU and NMS on LH secretion, as well as hypothalamic NMUR2 mRNA expression, in different experimental models. Intracerebral administration of NMU or NMS stimulated basal LH secretion in peripubertal male and female rats, as well as in cyclic females at diestrous (i.e. low levels of circulating LH). On the contrary, NMU failed to alter the stimulated levels of LH at the afternoon of proestrus (at 18:00), while it decreased the elevated LH levels in male rats after orchidectomy or KiSS-1 injection. In addition, expression analyses revealed that NMU2R mRNA significantly varied during postnatal sexual development and along the estrous cycle. In summary, our present data substantiate the potential role of NMU and NMS as novel regulators of gonadotropin secretion, and suggest the potential implication of these neuropeptides in the joint control of energy balance and reproductive function.

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