Pinealectomy produced adrenal hypertrophy in male mice. Melatonin not only reversed this effect, but also caused adrenal hypotrophy, by itself. Pinealectomy also augmented adrenal enlargement due to castration in males, but only the portion of hypertrophy due to pinealectomy was reversed by melatonin. Unilateral adrenalectomy was followed by adrenal enlargement 3 days later in males and females. This effect was reversed in males by melatonin, and in females by melatonin, 5-hydroxy-tryptamine, N-acetyl-5-hydroxytryptamine, 5-hydroxytryptophol, 5-methoxytryptophol, and 5-hydroxyindoleacetic acid; less so by 6-hydroxymelatonin; and not at all by 5-hydroxytryptophan or 5-methoxyindoleacetic acid (administered in single doses of 100 µg on the day of operation). Castration gave rise to increased adrenal weight in males, which was not significantly counteracted by melatonin. Adrenals were enlarged in males subjected to an ambient temperature of 5 °C for 4 h on each of 3 successive days, with no amelioration in adrenal weight response when
Continuing investigation of pineal gland function indicates that the anti-gonadotrophic activity of this organ cannot be attributed solely to the postulated hormone melatonin, the concentration of which is negligible in the pineal body compared to quantities required to produce unequivocal physiological effects. A non-melatonin antigonadotrophic substance recently isolated from bovine pineal glands was further purified by organic solvent extraction, ultrafiltration and gel filtration. Studies of partial blockage of compensatory ovarian hypertrophy in unilaterally ovariectomized Charles River CD-1 mice indicated that this substance is significantly more potent than melatonin in this test system.
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 microgram 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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