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

Abstract

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.

Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis

“…The crosstalk between pineal and adrenal glands is shown by melatonin's inhibitory effect on the ACTH-driven adrenal glucocorticoid production [19,20] and by the glucocorticoid-mediated regulation of pineal melatonin synthesis. Corticosterone may either potentiate or inhibit melatonin production when cultured pineal glands are stimulated by a low [9,21] or a high [22] concentration of noradrenaline, respectively.…”

La melatonina reduce la respuesta de cortisol al ACTH en humanos

“…En cambio detectamos la expresión de mARN para el receptor MT1 y MT2 en el tejido humano renal como ha sido previamente publicado 21 y fue usado como control positivo. Estos resultados son similares a los observados por nosotros en la corteza suprarrenal de la rata y del mono capuchino [8][9][10] .…”

“…En humanos, ambos receptores de melatonina están presentes en tejidos esteroidogé-nicos como la placenta y células de la granulosa 4,5 . Adicionalmente, estudios realizados en animales demuestran la presencia solo del receptor MT1 en las células de Leydig de la rata y hamster y en la glándula suprarrenal de rata adulta y de fetos y adultos de primates no humanos [6][7][8][9][10] . En esta última glándula, la melatonina inhibe la expresión de genes circadianos 11 y también la producción de cortisol estimulada por ACTH 9,10 .…”

Nycthemeral variation in melatonin receptor expression in the lymphoid organs of a tropical seasonal breeder Funambulus pennanti

“…Pineal melatonin levels, 2-[I 125 ] melatonin binding and other relevant molecular studies present a prominent 24 h rhythm in the density of melatonin receptors in the suprachiasmatic nuclei (SCN; Gerdin et al 2004;Masana et al 2000;Neu and Niles 1997), pars tuberalis of the pituitary (PT; Guerrero et al 2000) and other organs (Poon et al 1994;Roy et al 2001;Richter et al 2008;Yadav et al 2011), suggesting that melatonin regulates its own receptor availability which could be negatively correlated to the circulating levels of melatonin Neu and Niles 1997;Gauer et al 1994). As expected, melatonin receptor (MT1/MT2) expression was found to be upregulated during the light phase and downregulated during the dark phase of the light-dark cycle.…”