Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P1099

ICEECE2012 Poster Presentations Neuroendocrinology (83 abstracts)

Stimulatory role of neurokinin B in the control of the gonadotropic axis in the rat: developmental changes, sexual dimorphism and regulation by gonadal steroids

F. Ruiz-Pino 1, , V. Navarro 1, , A. Bentsen 5 , M. Sanchez-Garrido 1, , D. Garcia-Galiano 1, , M. Manfredi-Lozano 1, , S. Leon 1, , D. Clifton 4 , R. Steiner 4 , J. Mikkelsen 5 , L. Pinilla 1, & M. Tena-Sempere 1,


1University of Cordoba, Cordoba, Spain; 2CIBERobn, Cordoba, Spain; 3IMIBIC, Cordoba, Spain; 4University of Washington, Seattle, WA; 5Rigshospitalet, Copenhagen, Denmark.


Recent studies in various species have pointed out that Neurokinin B (NKB), encoded by Tac2 in rodents, and its receptor, NK3R, are important regulators of reproduction. NKB is co-expressed in Kiss1 neurons of the arcuate nucleus (ARC) and stimulates, via auto-regulatory loops, kisspeptin output onto GnRH neurons, therefore stimulating gonadotropin secretion. However, important aspects of the roles of NKB as regulators of the gonadotropic axis remain unknown. We report here that in the rat, LH secretory responses to the agonist of NKB, senktide, display sexual dimorphism, with greater responses in females regardless of the stage of postnatal maturation, and null NKB-induced LH secretion in males from puberty onwards. Such a sexual dimorphism manifested also in a higher number of NKB-positive neurons in the ARC in adult females. This may stem from differences in the sex steroid milieu during early critical periods of brain differentiation, as neonatal exposures to high doses of estrogen markedly decreased the number of NKB neurons and the circulating levels of LH, which were normalized by exogenous administration of senktide. Of note, estrogen also inhibited Tac2 expression in adult female rats in the ARC, while enhancing it in the lateral hypothalamus. Finally, despite null gonadotropic responses to senktide in adult male rats, adult females supplemented with testosterone retained LH responses to the NKB agonist. In sum, our study provides a comprehensive developmental analysis of the role of NKB in the control of the gonadotropic axis in the rat. Our observations disclose key aspects of this system, such as its maturational changes, sexual dimorphism and differential regulation by sex steroids, which may help to explain the spectrum of reproductive effects of the NKB system and the pathophysiological manifestations of its inactivation.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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