Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2017 Jul 1

PMID 28664358

Citations 9

Authors

Mohammad Saied Salehi

Homayoun Khazali

Fariba Mahmoudi

Mahyar Janahmadi

Affiliations

Soon will be listed here.

Abstract

The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

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References

Schulz R, Wilhelm A, Pirke K, Gramsch C, Herz A . Beta-endorphin and dynorphin control serum luteinizing hormone level in immature female rats. Nature. 1981; 294(5843):757-9. DOI: 10.1038/294757a0. View

Salehi M, Tamadon A, Jafarzadeh Shirazi M, Namavar M, Zamiri M . The Role of Arginine-Phenylalanine-Amide-Related Peptides in Mammalian Reproduction. Int J Fertil Steril. 2015; 9(3):268-76. PMC: 4671388. DOI: 10.22074/ijfs.2015.4540. View

Kriegsfeld L, Gibson E, Williams 3rd W, Zhao S, Mason A, Bentley G . The roles of RFamide-related peptide-3 in mammalian reproductive function and behaviour. J Neuroendocrinol. 2010; 22(7):692-700. PMC: 2908924. DOI: 10.1111/j.1365-2826.2010.02031.x. View

Rance N, Krajewski S, Smith M, Cholanian M, Dacks P . Neurokinin B and the hypothalamic regulation of reproduction. Brain Res. 2010; 1364:116-28. PMC: 2992576. DOI: 10.1016/j.brainres.2010.08.059. View

Wirth M, Gaffey A, Martinez B . Effects of intranasal oxytocin on steroid hormones in men and women. Neuropsychobiology. 2015; 71(4):202-11. DOI: 10.1159/000381023. View

Kinoshita F, Nakai Y, Katakami H, Imura H . Suppressive effect of dynorphin-(1-13) on luteinizing hormone release in conscious castrated rats. Life Sci. 1982; 30(22):1915-9. DOI: 10.1016/0024-3205(82)90472-6. View

Mikkelsen J, Simonneaux V . The neuroanatomy of the kisspeptin system in the mammalian brain. Peptides. 2008; 30(1):26-33. DOI: 10.1016/j.peptides.2008.09.004. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Caligioni C, Oliver C, Jamur M, Franci C . Presence of oxytocin receptors in the gonadotrophin-releasing hormone (GnRH) neurones in female rats: a possible direct action of oxytocin on GnRH neurones. J Neuroendocrinol. 2007; 19(6):439-48. DOI: 10.1111/j.1365-2826.2007.01550.x. View

10.

Navarro V, Castellano J, McConkey S, Pineda R, Ruiz-Pino F, Pinilla L . Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab. 2010; 300(1):E202-10. PMC: 3774070. DOI: 10.1152/ajpendo.00517.2010. View

11.

Selvage D, Johnston C . Interaction between norepinephrine, oxytocin, and nitric oxide in the stimulation of gonadotropin-releasing hormone release from proestrous rat basal hypothalamus explants. J Neuroendocrinol. 2004; 16(10):819-24. DOI: 10.1111/j.1365-2826.2004.01235.x. View

12.

Lukas M, Neumann I . Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats: social versus non-social effects. Neuropharmacology. 2011; 62(1):398-405. DOI: 10.1016/j.neuropharm.2011.08.016. View

13.

Neumann I, Maloumby R, Beiderbeck D, Lukas M, Landgraf R . Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology. 2013; 38(10):1985-93. DOI: 10.1016/j.psyneuen.2013.03.003. View

14.

Silverman R, MUNGER B, Halata Z . The sensory innervation of the rat rhinarium. Anat Rec. 1986; 214(2):210-25. DOI: 10.1002/ar.1092140217. View

15.

Veening J, Olivier B . Intranasal administration of oxytocin: behavioral and clinical effects, a review. Neurosci Biobehav Rev. 2013; 37(8):1445-65. PMC: 7112651. DOI: 10.1016/j.neubiorev.2013.04.012. View

16.

Ramaswamy S, Seminara S, Plant T . Evidence from the agonadal juvenile male rhesus monkey (Macaca mulatta) for the view that the action of neurokinin B to trigger gonadotropin-releasing hormone release is upstream from the kisspeptin receptor. Neuroendocrinology. 2011; 94(3):237-45. PMC: 3238032. DOI: 10.1159/000329045. View

17.

Goodman R, Coolen L, Anderson G, Hardy S, Valent M, Connors J . Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep. Endocrinology. 2004; 145(6):2959-67. DOI: 10.1210/en.2003-1305. View

18.

Johnston C, Lopez F, Samson W, Negro-Vilar A . Physiologically important role for central oxytocin in the preovulatory release of luteinizing hormone. Neurosci Lett. 1990; 120(2):256-8. DOI: 10.1016/0304-3940(90)90053-c. View

19.

Rettori V, Canteros G, Renoso R, Gimeno M, McCANN S . Oxytocin stimulates the release of luteinizing hormone-releasing hormone from medial basal hypothalamic explants by releasing nitric oxide. Proc Natl Acad Sci U S A. 1997; 94(6):2741-4. PMC: 20160. DOI: 10.1073/pnas.94.6.2741. View

20.

Grachev P, Millar R, OByrne K . The role of neurokinin B signalling in reproductive neuroendocrinology. Neuroendocrinology. 2013; 99(1):7-17. DOI: 10.1159/000357734. View