Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons

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.

Intrinsic links among sex, emotion, and reproduction

“…The endocrine effects of oxytocin include induction of uterine contractions during parturition and an essential role in the milk-ejection reflex during lactation [ 118 ]. Oxytocin receptors are also found on GnRH neurones [ 119 ] and intranasal administration of oxytocin to male rats results in increased GnRH mRNA expression in the anterior hypothalamus [ 120 ]. Conversely, vasopressin has an indirect inhibitory effect on GnRH through its potentiation of adrenocortico-tropic hormone (ACTH) [ 121 ] and cortisol secretion [ 122 ] (Fig.…”

Diet-Induced Obesity Elicits Macrophage Infiltration and Reduction in Spine Density in the Hypothalami of Male but Not Female Mice

“…Activity-dependent GnRH gene regulation by afferent neurons has been implied. Hypothalamic factors involved in reproductive function, such as RFamide-related peptide 3 (RFRP-3), a mammalian gonadotropin-inhibitory hormone ortholog; senktide, a neurokinin B receptor agonist; and oxytocin; elicit changes in LH serum levels, by altering both GnRH secretion and Gnrh transcription ( 85 – 87 ). On the other hand, GnRH neurons express cytokine receptors ( 88 ), and Gnrh may be repressed via activation of cytokine receptor signaling pathways.…”

Role of RF-amid Related Peptide-3 (RFRP-3) in Inhibitory Effect of Orexin A on Reproductive Function in the Animal Model of Male Wistar Rats

“…After that, the brain was removed very rapidly and the hypothalamus was isolated based on the following borders: rostral to the anterior border of the optic chiasm, caudal to the posterior border of the mammillary body, dorsal to the ventral border of the thalamus, and 2 mm lateral to the third ventricle Subsequently, the hypothalamus was immersed in liquid nitrogen immediately. It was stored under a temperature of − 80 °C until conducting further research [21].…”