Rhythmic Expression of Functional MT1 Melatonin Receptors in the Rat Adrenal Gland

Nov 28, 2007Endocrinology

Daily patterns of active melatonin receptors in the rat adrenal gland

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Abstract

The adult rat adrenal gland shows high amplitude diurnal variation in functional MT1 melatonin receptor expression.

MT1 melatonin receptor mRNA levels are higher during the day/night transition (1800-2200 h).
The predicted 37-kDa MT1 protein is present in adrenal glands collected at 2200 h but absent at 1000 h.
MT2 melatonin receptor mRNA and protein are not expressed in the rat adrenal gland.
High-affinity binding of melatonin is observed in adrenal membranes at 2200 h, with a dissociation constant of 14.22 +/- 1.23 pm.
Melatonin inhibits ACTH-stimulated corticosterone production in a time-dependent manner, which can be reversed by the receptor antagonist luzindole.

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We previously demonstrated that melatonin is involved in the regulation of adrenal glucocorticoid production in diurnal primates through activation of MT1 membrane-bound melatonin receptors. However, whether melatonin has a similar role in nocturnal rodents remains unclear. Using an integrative approach, here we show that the adult rat adrenal gland expresses a functional MT1 melatonin receptor in a rhythmic fashion. We found that: 1) expression of the cognate mRNA encoding for the MT1 membrane-bound melatonin receptor, displaying higher levels in the day/night transition (1800-2200 h); 2) expression of the predicted 37-kDa MT1 polypeptide in immunoblots from adrenals collected at 2200 h but not 1000 h; 3) no expression of the MT2 melatonin receptor mRNA and protein; 4) specific high-affinity 2-[(125)I]iodomelatonin binding in membrane fractions and frozen sections from adrenals collected at 2200 h but not 0800 h (dissociation constant = 14.22 +/- 1.23 pm; maximal binding capacity = 0.88 +/- 0.02 fmol/mg protein); and 5) in vitro clock time-dependent inhibition of ACTH-stimulated corticosterone production by 1-100 nm melatonin, which was reversed by 1 microm luzindole (a melatonin membrane receptor antagonist). Our findings indicate not only expression but also high amplitude diurnal variation of functional MT1 melatonin receptors in the rat adrenal gland. It is conceivable that plasma melatonin may play a role to fine-tune corticosterone production in nocturnal rodents, probably contributing to the down slope of the corticosterone rhythm.

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Rhythmic Expression of Functional MT1 Melatonin Receptors in the Rat Adrenal Gland

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