Male and female hamsters were maintained on a long photoperiod (14L:10D) and were divided into the following groups: group 1, injected with vehicle at both 11.00 and 17.00 h; groups 2–5, injected with various doses of melatonin at 11.00 h (0, 100 μg, 500 μg, 1 mg) and 25 g of melatonin at 17.00 h. In males, a.m. vehicle p.m. melatonin treatment for 70 days led to atrophy of the testes and accessory sex organs and to a significant depression of both plasma LH and PRL titers. There was a graded inhibition of these actions of exogenous melatonin in animals receiving 100 μg, 500 μg or 1 mg a.m. injections of melatonin with 1 mg completely preventing the effects of p.m. melatonin. 80% of the female hamsters receiving daily p.m. injections of melatonin for 9 weeks became acyclic with significant decreases in uterine weight and increases in ovarian weight. All doses of melatonin given at 11.00 h suppressed the inhibitory actions of p.m. melatonin with the exception of vaginal cyclicity for which 500 μg or more was required to restore normal vaginal cyclicity in all animals. These results demonstrate that morning injections of melatonin can prevent the antigonadotropic effects of afternoon melatonin injections and provide support for the hypothesis that the paradoxical actions of melatonin may be related to the ability of the indole to regulate its own receptors.

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