Central Orexin A Affects Reproductive Axis by Modulation of Hypothalamic Kisspeptin/Neurokinin B/Dynorphin Secreting Neurons in the Male Wistar Rats
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It is an established fact that orexin plays an important role in regulating the reproductive axis and the secretions of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular mechanisms are not fully recognized. Accordingly, the aim of the present study is to find out whether the central injection of orexin A (OXA) and its antagonists, SB-334867 (as orexin receptor antagonist 1; OX1RA) and JNJ-10397049 (as orexin receptor antagonist 2; OX2RA), either alone or in combination, can leave any impact on the reproductive axis (either hormonal or behavioral) in the male Wistar rats. Furthermore, in order to see whether OXA signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin (known as KNDy neurons, a neural network which works upstream of GnRH neurons) or not, the relative gene expression of these neuropeptides were measured. Overall, the data from radioimmunoassay revealed that OXA significantly decreases the mean serum level of LH and testosterone and, in a similar vein, its antagonists neutralize this impact. Moreover, data from real-time quantitative PCR indicated that OXA has significantly reduced the hypothalamic expression of Gnrh. In this line, the gene expressions of Kisspeptin and Neurokinin b decreased. However, OXA antagonists neutralize this impact. Also, the expression of Dynorphin gene was upregulated by the following application of the OXA. The results of this study are related to the impact of orexin on the reproductive axis. It is recommended that KNDy neurons as the interneural pathway relay the information of orexin to the GnRH neurons.
KeywordsOrexin Kisspeptin Gonadotropin-releasing hormone Luteinizing hormone KNDy neurons
Hereby the authors confirm that there is no conflict of interests in the present research. This research is supported financially by grant from Shahid Beheshti University.
- Amstalden, M., Coolen, L. M., Hemmerle, A. M., Billings, H. J., Connors, J. M., Goodman, R. L., et al. (2010). Neurokinin 3 receptor immunoreactivity in the septal region, preoptic area and hypothalamus of the female sheep: Colocalisation in neurokinin B cells of the arcuate nucleus but not in gonadotrophin-releasing hormone neurones. Journal of Neuroendocrinology, 22(1), 1–12. https://doi.org/10.1111/j.1365-2826.2009.01930.x.CrossRefPubMedGoogle Scholar
- Czerwinska, J., Chojnowska, K., Kaminski, T., Bogacka, I., Smolinska, N., & Kaminska, B. (2017). Orexin receptor expression in the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes of free-living European beavers (Castor fiber L.) in different periods of the reproductive cycle. General and Comparative Endocrinology, 240, 103–113. https://doi.org/10.1016/j.ygcen.2016.09.013.CrossRefPubMedGoogle Scholar
- Goodman, R. L., Lehman, M. N., Smith, J. T., Coolen, L. M., de Oliveira, C. V., Jafarzadehshirazi, M. R., et al. (2007). Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology, 148(12), 5752–5760. https://doi.org/10.1210/en.2007-0961.CrossRefPubMedGoogle Scholar
- Hunt, N. J., Waters, K. A., & Machaalani, R. (2017). Promotion of the unfolding protein response in orexin/dynorphin neurons in sudden infant death syndrome (SIDS): Elevated pPERK and ATF4 expression. Molecular Neurobiology, 54(9), 7171–7185. https://doi.org/10.1007/s12035-016-0234-3.CrossRefPubMedGoogle Scholar
- Irahara, M., Tamura, T., Matuzaki, T., Saito, S., Yasui, T., Yamano, S., et al. (2001). Orexin-A suppresses the pulsatile secretion of luteinizing hormone via beta-endorphin. Biochemical and Biophysical Research Communications, 281(1), 232–236. https://doi.org/10.1006/bbrc.2001.4328.CrossRefPubMedGoogle Scholar
- Iwasa, T., Matsuzaki, T., Kiyokawa, M., Shimizu, F., Minakuchi, M., Kuwahara, A., et al. (2007). The type 2 corticotrophin-releasing hormone receptor mediates orexin A-induced luteinising hormone suppression in ovariectomised rats. Journal of Neuroendocrinology, 19(9), 732–738. https://doi.org/10.1111/j.1365-2826.2007.01583.x.CrossRefPubMedGoogle Scholar
- Lehman, M. N., Coolen, L. M., & Goodman, R. L. (2010). Minireview: Kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: A central node in the control of gonadotropin-releasing hormone secretion. Endocrinology, 151(8), 3479–3489. https://doi.org/10.1210/en.2010-0022.CrossRefPubMedPubMedCentralGoogle Scholar
- Navarro, V. M., Castellano, J. M., McConkey, S. M., Pineda, R., Ruiz-Pino, F., Pinilla, L., et al. (2011). Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. American Journal of Physiology-Endocrinology and Metabolism, 300(1), E202–E210. https://doi.org/10.1152/ajpendo.00517.2010.CrossRefPubMedGoogle Scholar
- Paxinos, G., & Watson, C. (2014). Paxinos and Watson’s the rat brain in stereotaxic coordinates (7th edn.). London: Academic Press.Google Scholar
- Tamura, T., Irahara, M., Tezuka, M., Kiyokawa, M., & Aono, T. (1999). Orexins, orexigenic hypothalamic neuropeptides, suppress the pulsatile secretion of luteinizing hormone in ovariectomized female rats. Biochemical and Biophysical Research Communications, 264(3), 759–762. https://doi.org/10.1006/bbrc.1999.1573.CrossRefPubMedGoogle Scholar