Orexin A and B in vitro modify orexins receptors expression and Gonadotropins secretion of anterior pituitary cells of proestrous rats

Abstract

Orexin A and orexin B (hypocretins) are neuropeptidessynthesized mainly by neurons located in the lateral hypothalamus andprojections throughout the brain. They are agonists at both the orexin 1and orexin 2 G protein-coupled receptors. They have been related toarousal, sleep and feeding, autonomic and neuroendocrine functions. Theirrole in the brain control of gonadotropins secretion was postulated inrodents and humans. Previously, we demonstrated the participation of theorexinergic system in attaining successful reproduction in in vivostudies. Methods: We studied in vitro the effects of both neuropeptides, in thepresence or absence of selective antagonists, on the mRNA expression oforexin 1 and orexin 2 receptors in anterior pituitary cells of proestrousrats, as well as the direct effects on FSH and LH secretion. Results: Both orexin A and orexin B increased FSH and LH secretion, theseeffects was suppressed by the orexin 1 receptor blocking agent SB-334867and the orexin 2 receptor antagonists JNJ-10397049. Orexin A and orexin Bdecreased of OX1 receptor mRNA expression and this effect was modifiedonly when both blocking agent were present. Neither orexin A nor theblocking drugs by themselves modified OX2 receptor mRNA expression.Orexin B treatment increased the mRNA expression of OX2 receptor. Theeffect was abolished only by the OX2 receptor antagonist. Conclusion: In an in vitro model, we demonstrated a direct effect oforexins on gonadotropins release and orexins receptors expression,underling the hypothesis that orexins participate in the brain control ofpituitary functions.