Melatonin transmits photoperiodic signals that regulate reproduction. Two melatonin receptors (MT1 and MT2) have been cloned in mammals and additional melatonin binding sites suggested, but the receptor that mediates the effects of melatonin on the photoperiodic gonadal response has not yet been identified. We therefore investigated in mice whether and how targeted disruption of MT1, MT2, or both receptor types affects the expression level of two key genes for the photoperiodic gonadal regulation, type 2 and 3 deiodinase (Dio2 and Dio3, respectively). These are expressed in the ependymal cell layer lining the infundibular recess of the third ventricle and regulated by thyrotropin produced in the pars tuberalis. In wild-type C3H mice, Dio2 expression was constantly low, and no photoperiodic changes were observed, whereas Dio3 expression was upregulated under short-day conditions. In C3H with targeted disruption of MT1 and MT1/MT2, Dio2 expression was constitutively upregulated, Dio3 expression was constitutively downregulated, and the photoperiodic effect on Dio3 expression was abolished. Under short-day conditions, C3H with targeted disruption of MT2 displayed similar expression levels of Dio2 and Dio3 as wild-type animals, but they responded to long-day condition with a stronger suppression of Dio3 than wild-type mice. Melatonin injections into wild-type C57BL mice suppressed Dio2 expression and induced Dio3 expression under long-day conditions. These effects were abolished in C57BL mice with targeted disruption of MT1. All data suggest that the melatonin signal that transmits photoperiodic information to the hypothalamo-hypophysial axis acts on the MT1 receptor.
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