Maternal melatonin communicates daylength information to the fetus in Siberian hamsters. Fetal sensitivity to melatonin declines near birth. In this report, we describe melatonin receptor distribution and a second messenger response to melatonin in Siberian hamsters during the perinatal period. The sites of high-affinity 2-[125I]iodomelatonin ([125I]MEL) binding were generally similar throughout the perinatal period. The non-hydrolyzable GTP analog, guanosine-5'-O-(3-thiotriphosphate) (100 microM) inhibited [125I]MEL binding at each age, suggesting the melatonin receptors are associated with guanine nucleotide binding proteins (G proteins). Furthermore, melatonin (10 nM) inhibited forskolin-stimulated cAMP accumulation in median eminence/pars tuberalis (ME/PT) explants as early as 4 days before birth, when sensitivity to melatonin in vivo is high. The cAMP regulatory system appeared disrupted on the day of birth, in that forskolin (10 microM) stimulation of cAMP accumulation was reduced, and melatonin did not inhibit cAMP accumulation stimulated by forskolin. A higher forskolin dose (100 microM) elevated cAMP levels more clearly on the day of birth, and melatonin inhibited forskolin-stimulated cAMP accumulation. These results suggest that the decreased physiological responsiveness to melatonin at the end of gestation may be due to alterations in the cAMP regulatory system.