Objectives: 

Membrane (MT1 and MT2) and nuclear (RORalpha) melatonin receptors have been identified in rat liver, but not data regarding their regulation exist to date. Herein, we studied the distribution of these receptors over a 24 hr period and the role of melatonin on their regulation.

Materials: 

Male Wistar rats were housed in a 12:12 hr light/dark cycle. Shan-pinealectomized (SPx) and pinealectomized (Px) animals were sacrificed at 08, 12, 16, 20, 24, 02, 04, 06 hr, and liver were collected and used for preparation of nuclei and cytosol to evaluate the expression and density of the receptors by RT-PCR and Western-blot, respectively. In addition, different doses (10, 40 and 200 mg/kg) of melatonin were intraperitoneally injected to the animals for evaluating their effects on the regulation of these receptors. Data are expressed as the means ± SEM and one-way ANOVA with a post-hoc test were used for statistics.

Results: 

The highest expression and density levels of MT1/MT2 melatonin receptors occur at night, while Px blunted their nocturnal upregulation. In contrast, Px increased the expression and density of the nuclear receptors of melatonin. Melatonin administration induces an increase in the expression and density of membrane, but not nuclear receptors.

Conclusions: 

We reported here for the first time the existence of a daily variation in the distribution of MT1/MT2 melatonin receptors, which peak at night. The absence of melatonin, as assessed by Px, blunts the nocturnal increase in these receptors expression, while increases RORalpha nuclear receptors expression. These data, together with the melatonin-induced receptor expression, suggest that pineal melatonin regulates the daily fluctuations of its peripheral receptors in rat liver.