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Background:  Kisspeptin-GPR54 system stimulates the hypothalamus-pituitary-gonadal (HPG) axis; dysfunction of the gene encoding the GPR54 receptor causes hypogonadism and infertility. Opioid peptides inhibit the reproductive axis. Peptide 234 is a GPR54 receptor antagonist and blocks the stimulatory effects of kisspeptin on HPG axis.    Objectives:  Interactions of morphine, kisspeptin and peptide 234 on mean plasma testosterone concentration was investigated in rats. .    Materials and Methods:  In the present experimental study, seventy male Wistar rats in 14 groups (n = 5 in each group) received saline, different doses of kisspeptin (100 pmol, 1 or 3 nmol, Intracerebroventricular (ICV)), P234 (1 or 2.5 nmol) or Co- administration of kisspeptin, P234, morphine and naloxone at 09:00 - 09:30 am. In the co-administrated groups, kisspeptin was injected at 15 min following P234, morphine or naloxone injections. Blood samples were collected 60 min following injections. Plasma testosterone concentration was measured using the rat testosterone ELISA kit.    Results:  Injections of kisspeptin (1 or 3 nmol) significantly increased the mean testosterone concentration compared to saline. Injection of different doses of P234 (1 or 2.5nmol) did not significantly decrease mean testosterone compared to saline. Co-administration of kisspeptin and different doses of P234 significantly decreased mean testosterone concentration compared to the kisspeptin group. Co-administration of P234/morphine or P234/naloxone significantly decreased mean testosterone concentration compared to kisspeptin/saline, kisspeptin/morphine or kisspeptin/ naloxone groups.    Conclusions:  Morphine and kisspeptin/GPR54 signaling pathway may interact with each other to control the hypothalamic-pituitary-gonadal axis.

Interactions of Morphine and Peptide 234 on Mean Plasma Testosterone Concentration