Adult, Charles River CD-1, male mice were housed in an environmental control chamber under strict conditions of controlled light (12D/12L) and temperature. The mice were sacrificed at various times throughout the twenty-four hour clock and their pineals prepared routinely for electron microscopy. The number of dense-cored or granulated vesicles present in the polar terminals of pinealocytes were quantitated in thin cross sections through pericapillary areas. A distinct circadian rhythm was observed in the number of granulated vesicles with a three- to four-fold difference between late photoperiod maximum and late dark period minimum. The rhythm was abolished by bilateral superior cervical ganglionectomy. These results are consistent with the hypothesis that the granulated vesicles are synthesized and stored in the pinealocytic cytoplasm during the photoperiod under the tropic influence of norepinephrine, and are released during the dark period when melatonin synthesis is greatest. Melatonin, administered as daily intraperitoneal doses of 50 μg over a period of five days, was observed to increase markedly the number of pinealocytic granulated vesicles during the light period, but led during the dark period to a decrease in their numbers to levels below that of diluent-treated controls. It may be that melatonin stimulates the synthesis and/or release of granulated vesicles which represent the packaged form of a major secretory product
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