Effect of Melatonin on the Response of the Thyroid to Thyrotropin Stimulationin Vitro

Abstract

Thyroidal–melatonin interactions are of particular importance to amphibian development since the thyroid controls the progress of metamorphosis while melatonin may coordinate its rate with prevailing environmental conditions. Melatonin antagonized thyroxine (T4) action at the tissue level and directly inhibited baseline T4secretion in culture, so the present work sought to determine if it antagonized the response of the thyroid to thyroid stimulating hormone (TSH) as well. A preliminary experiment showed that, inRana pipiens,the concentration of TSH (0.2 μg/ml) used in the culture of tadpole thyroids stimulated T4secretion as much as frog pituitaries, but more than late premetamorphic tadpole pituitaries. There was no significant effect of 1 to 15 μg/ml melatonin in TSH-containing thyroid cultures of variousRanaspecies of tadpoles and frogs in experiments with media collected once every 24 or 48 hr, although 15 μg/ml melatonin tended to depress T4secretion. In a final experiment, a higher melatonin concentration was used as well as more frequent media collections. Thyroids from prometamorphicRana catesbeianatadpoles were cultured in L-15 media with periodic stimulation by 0.2 μg/ml TSH, or TSH and 10 or 100 μg/ml melatonin. Media were collected at the end of two 3-hr TSH pulses, and every 8 hr thereafter for the next 3 days. Melatonin was administered until the end of Day 2 while TSH was given only on Day 2 in addition to the original 3-hr pulses. The secretion of T4was inhibited significantly by 10 μg/ml melatonin at only two of the early media collections. In contrast, 100 μg/ml melatonin significantly depressed T4secretion in response to TSH at all but one interval and completely inhibited the thyroidal response to TSH reintroduced into the media on Day 2. The findings suggest that a high concentration of melatonin is inhibitory to the thyroidal response to TSH, but that lower concentrations do not significantly overcome the TSH stimulus.