Cryptochrome 2 Expression Level Is Critical for Adrenocorticotropin Stimulation of Cortisol Production in the Capuchin Monkey Adrenal

Torres-Farfan, C; Abarzua-Catalan, L; Valenzuela, FJ; Mendez, N.; Richter, HG; Valenzuela GJ; Seron-Ferre, M

Abstract

Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression hasbeenreported in the adrenal cortex of several species. However, there arenoreports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nM ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3'-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at themRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3'-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH. Copyright © 2009 by The Endocrine Society.

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Título según WOS: Cryptochrome 2 Expression Level Is Critical for Adrenocorticotropin Stimulation of Cortisol Production in the Capuchin Monkey Adrenal
Título según SCOPUS: Cryptochrome 2 expression level is critical for adrenocorticotropin stimulation of cortisol production in the capuchin monkey adrenal
Título de la Revista: ENDOCRINOLOGY
Volumen: 150
Número: 6
Editorial: OXFORD UNIV PRESS INC
Fecha de publicación: 2009
Página de inicio: 2717
Página final: 2722
Idioma: English
URL: http://press.endocrine.org/doi/abs/10.1210/en.2008-1683
DOI:

10.1210/en.2008-1683

Notas: ISI, SCOPUS