Melatonina inhibe la respuesta de cortisol a ACTH: posible mediación a través del gen reloj Per1 / Melatonin inhibition of the cortisol response to ACTH may be exerted through period circadian protein homolog 1 (Per1)

ABSTRACT

Background: Circadian cortisol production results from the interaction of the circadian production of ACTH, the autonomic nervous system and intrinsic factors within the gland. An additional regulator is the neuro-hormone melatonin. In human adrenal gland cultures, melatonin inhibited ACTH stimulated cortisol production and Per1 mRNA expression. ACTH actions on the adrenal involve early and late responses. Aim: To investigate the effects of melatonin on the time course of ACTH stimulated cortisol production and of Per1 expression in the lamb adrenal gland. Material and Methods: Adrenal glands and plasma of five newborn lambs were obtained. Adrenal glands were cut in 15 mg explants. Three of these explants were stored for RNA extraction. The rest of explants were using in different culture protocols with ACTH and melatonin. Results: Lambs had an in vivo a circadian variation in plasma cortisol and in adrenal Per1 expression. In vitro, ACTH stimulated an early and late increase in cortisol production and an early increase in Per1 expression reaching a maximum at 3 hours of treatment. Melatonin inhibited the early Per1 response to ACTH without affecting the early ACTH stimulated cortisol production. However, melatonin inhibited the late response of cortisol production to ACTH. Conclusions: The inhibitory actions of melatonin on Per1 response to ACTH may contribute to the inhibitory effects of melatonin on adrenal steroidogenic response to ACTH.