Abstract
Melatonin is synthesized and released following a circadian rhythm and reaches its highest blood levels during the night. It relays signals of darkness to target tissues involved in regulating circadian and seasonal rhythms. Here, we report the expression of human melatonin receptors type 1 and 2 (hMT 1 and hMT 2, respectively) in Chinese hamster ovary (CHO) cells following exposure to melatonin treatments mimicking the amplitude (400 pM) and duration (8 hr) of the nightly melatonin peak and upon withdrawal. Exposure of CHO-MT 1 cells to melatonin (400 pM) for 0.5, 1, 2, 4, and 8 hr significantly increased specific 2-[ 125 I ]iodomelatonin (500 pM) binding to hMT 1 melatonin receptors upon 16-hr withdrawal. However, the same treatment did not affect the expression of hMT 2 melatonin receptors. The increase in specific 2-[ 125 I ]iodomelatonin (500 pM) binding (162±29%, N=3, P<0.05) 16 hr after melatonin withdrawal was parallel to increases in hMT 1 melatonin receptor mRNA (231±33%, N=4, P<0.05). This effect was due to an increase in the total number of hMT 1 receptors [ B max 833±97 fmol/mg protein (N=3), control; 1449±41 fmol/mg protein (N=3), treated], with no change in binding affinity. The melatonin-mediated increase in MT 1 melatonin receptor expression upon withdrawal was not mediated through either a direct effect of the hormone in the promoter’s vector or in the rate of mRNA degradation. In conclusion, melatonin differentially regulates the expression of its own receptors, which may have important implications in the transduction of dark signals in vivo.
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