Effects of Melatonin Agonists and Antagonists on Reproduction and Body Weight in the Siberian Hamster

Abstract

This study examined whether melatonin-induced inhibition of testicular weight and body weight in vivo could be antagonized by luzindole, a competitive melatonin receptor antagonist, or methysergide, a competitive serotonin receptor antagonist. Adult male Siberian hamsters were exposed to a long photoperiod (16L:8D) and given daily injections of drugs 3 h before lights off for 7 weeks. Hamsters treated with melatonin (0.375 mg/kg) exhibited testicular regression and loss of body weight. These effects were also marked in hamsters treated concomitantly with melatonin (0.375 mg/kg) and luzindole (10 mg/kg). In other studies, chronic injections of luzindole (30 mg/kg) to juvenile hamster failed to antagonize testicular regression induced by either melatonin injections or exposure to a short day photoperiod (12L: 12D). In contrast, concommitant injections of methysergide (6.25 mg/kg) and melatonin attenuated testicular regression and loss of body weight. When administered alone, neither luzindole nor methysergide affected testicular weight or body weight, whereas chronic injections of 5-methyoxyluzindole (10 mg/kg) mimicked the inhibitory effects of melatonin. 5-Methoxyluzindole inhibits 2-[125I]-iodomelatonin binding to median eminence/pars tuberalis membranes with an affinity similar to that of melatonin. Luzindole shows lower affinity for the inhibition of 2-[125I]-iodomelatonin binding than melatonin, which may explain why luzindole is not an effective melatonin receptor antagonist when administered in vivo. Methysergide, which has a very low affinity for inhibition of 2-[125I]-iodomelatonin binding, probably inhibits the effects of melatonin by blocking serotonergic neurotransmission.

Acute modulation of somatostatin receptor function by melatonin in the rat frontoparietal cortex

“…The melatonin effect was not blunted by the melatonin receptor antagonist luzindole. In this regard, Duncan et al [1990] found that concomitant administration of luzindole did not inhibit the antigonadal effects of melatonin. Several different factors may have contributed to the ineffectiveness of luzindole in the present study.…”

“…This biphasic effect is due to the activation of Gi and compound to be very low. In the Siberian hamster, the affinity of melatonin for its receptors is much greater than that of luzindole [Duncan et al, 1990]. This may also help to explain why luzindole does not antagonize the effect of melatonin in the rat frontoparietal cortex.…”

MT1 Melatonin Receptors Mediate Somatic, Behavioral, and Reproductive Neuroendocrine Responses to Photoperiod and Melatonin in Siberian Hamsters (Phodopus sungorus)

“…High doses (30 mg/kg) of luzindole, an MT1/MT2 antagonist/inverse agonist, were without effect on hamster reproductive responses to photoperiod or MEL (11), suggesting that disruption of MEL signaling at MT1/MT2 receptors is compatible with normal photoperiodic responses. In contrast, late afternoon injections of MEL elicit changes in ependymal cell layer expression of type II and type III iodothyronine deiodinase mRNA (Dio2 and Dio3, respectively) in wild-type mice but fail to do so in mice with targeted disruption of the MT1 receptor (12).…”

A comparative study of picomolar affinity 2-[125I]iodomelatonin binding sites in the hearts of three salmonid species

“…Melatonin is known for its modulatory role in gonadal development and reproduction in rodents (Duncan 1990;Reiter 1987), birds (Ralph 1970) as well as fish (Garg 1988). Its direct action on the gonads was also implicated in a few reports (Ayre 1992;Wang 1992).…”