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Clock Gene Expression in Adult Primate Suprachiasmatic Nuclei and Adrenal: Is the Adrenal a Peripheral Clock Responsive to Melatonin?

Programa de Fisiopatología (F.J.V., C.T.-F., N.M., M.S.-F.), Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 16038, Chile; Departamento de Ciencias Fisiológicas (C.T.-F., F.T., M.S.-F.), Facultad de Ciencias Biológicas, and Departamento de Endocrinología (C.C.), Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Instituto de Anatomía, Histología, y Patología (H.G.R.), Facultad de Medicina, Universidad Austral de Chile; Department of Women’s Health (G.J.V.), Arrowhead Regional Medical Center, Colton, California 92324; and Universidad de Tarapaca and Centro de Investigaciones del Hombre del Desierto (M.S.-F.), Casilla 6-D Arica, Chile

Address all correspondence and requests for reprints to: María Serón-Ferré, Ph.D., Salvador 486, Providencia, Santiago, Chile; or Departamento de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 16038, Santiago 9, Chile. E-mail: mseron{at}med.uchile.cl.

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nM melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.

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