A Circadian Clock Entrained by Melatonin Is Ticking in the Rat Fetal Adrenal

• Published in: Endocrinology (Philadelphia) 2011-05, Vol.152 (5), p.1891-1900
• Main Authors: Torres-Farfan, C, Mendez, N, Abarzua-Catalan, L, Vilches, N, Valenzuela, G. J, Seron-Ferre, M
• Format: Article
• Language: English
• Subjects: Adrenal glands; Adrenal Glands - drug effects; Adrenal Glands - embryology; Adrenal Glands - metabolism; Analysis of Variance; Animals; ARNTL Transcription Factors - genetics; Biological and medical sciences; Biological clocks; Chronobiology; Circadian Clocks - genetics; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Corticosterone; Corticosterone - blood; Corticosterone - metabolism; Early Growth Response Protein 1 - genetics; EGR-1 protein; Energy intake; Entrainment; Female; Fetuses; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Genes; In Vitro Techniques; Male; Melatonin; Melatonin - blood; Melatonin - pharmacology; Period Circadian Proteins - genetics; Phosphoproteins - genetics; Pregnancy; Proteins; Rats; Rats, Sprague-Dawley; Receptor, Melatonin, MT1 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Steroidogenic acute regulatory protein; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2010-1260

The rat fetal adrenal contains an autonomous circadian clock, potentially regulated by maternal melatonin. The adrenal gland in the adult is a peripheral circadian clock involved in the coordination of energy intake and expenditure, required for adaptation to the external environment. During fetal life, a peripheral circadian clock is present in the nonhuman primate adrenal gland. Whether this extends to the fetal adrenal gland like the rat is unknown. Here we explored in vivo and in vitro whether the rat fetal adrenal is a peripheral circadian clock entrained by melatonin. We measured the 24-h changes in adrenal content of corticosterone and in the expression of clock genes Per-2 and Bmal-1 and of steroidogenic acute regulatory protein (StAR), Mt1 melatonin receptor, and early growth response protein 1 (Egr-1) expression. In culture, we explored whether oscillatory expression of these genes persisted during 48 h and the effect of a 4-h melatonin pulse on their expression. In vivo, the rat fetal adrenal gland showed circadian expression of Bmal-1 and Per-2 in antiphase (acrophases at 2200 and 1300 h, respectively) as well as of Mt1 and Egr-1. This was accompanied by circadian rhythms of corticosterone content and of StAR expression both peaking at 0600 h. The 24-h oscillatory expression of Bmal-1, Per-2, StAR, Mt1, and Egr-1 persisted during 48 h in culture; however, the antiphase between Per-2 and Bmal-1 was lost. The pulse of melatonin shifted the acrophases of all the genes studied and restored the antiphase between Per-2 and Bmal-1. Thus, in the rat, the fetal adrenal is a strong peripheral clock potentially amenable to regulation by maternal melatonin.