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

Aim

Orexin A and orexin B (hypocretins) are neuropeptides synthesized mainly by neurons located in the lateral hypothalamus and projections throughout the brain. They are agonists at both the orexin 1 and orexin 2 G protein-coupled receptors. They have been related to arousal, sleep and feeding, autonomic and neuroendocrine functions. Their role in the brain control of gonadotropins secretion was postulated in rodents and humans. Previously, we demonstrated the participation of the orexinergic system in attaining successful reproduction in in vivo studies.

Methods

We studied in vitro the effects of both neuropeptides, in the presence or absence of selective antagonists, on the mRNA expression of orexin 1 and orexin 2 receptors in anterior pituitary cells of proestrous rats, as well as the direct effects on FSH and LH secretion.

Results

Both orexin A and orexin B increased FSH and LH secretion; these effects were suppressed by the orexin 1 receptor blocking agent SB-334867 and the orexin 2 receptor antagonists JNJ-10397049. Orexin A and orexin B decreased OX1 receptor mRNA expression and this effect was modified only when both blocking agents were present. Neither orexin A nor the blocking drugs by themselves modified OX2 receptor mRNA expression. Orexin B treatment increased the mRNA expression of OX2 receptor. The effect was abolished only by the OX2 receptor antagonist.

Conclusion

In an in vitro model, we demonstrated a direct effect of orexins on gonadotropins release and orexins receptors expression, underlining the hypothesis that orexins participate in the brain control of pituitary functions.