Melatonin Inhibits the Basal and TSH-Stimulated Mitotic Activity of Thyroid Follicular Cells In Vivo and in Organ Culture

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Abstract
The aim of the present study has been to examine the effect of melatonin, administered to mice as daily subcutaneous injections for a total of 10 days, on the mitotic activity of thyroid follicular cells (TFC). The colchicine metaphase-arrest technique was employed in the experiment. We found that melatonin (10 .mu.g and/or 100 .mu.g injection) decreased significantly the mean mitotic activity rate (MMAR) of TFC in both male and female mice. Moreover, melatonin totally suppressed the stimulatory effect of TSH on the MMAR of TFC in both sexes of mice. Furthermore, the effect of melatonin (5 .times. 10-7 M) on the proliferation of TFC in the organ-cultured rat and mouse thyroid explants was investigated. It was found that melatonin almost totally suppressed the MMAR of TFC in organ culture. Moreover, melatonin blocked the stimulatory effect of TSH on the MMAR of TFC in both rat and mouse thyroid explants. N-actylserotonin (NAc-5HT, 10-6 M) also decreased the MMAR of cultured thyroid explants, but its effect was less expressed when compared to melatonin inhibition. The present data indicate that melatonin can exert its inhibitory effect on the proliferation of TFC directly at the thyroid level, since this pineal indoleamine has been shown to suppress not only basal but also TSH-stimulated mitotic activity. The results are in agreement with the hypothesis of a pineal-thyroid negative feedback, assuming the direct inhibitory effect of melatonin on the thyroid growth.