Molecular and Cellular Endocrinology 186 (2002) 169 – 173 Perinatal neuroendocrine regulation. Development of the circadian time-keeping system Marı ´a Sero ´ n-Ferre ´ a, *, Claudia Torres a , Victor Hugo Parraguez b , Marcela Vergara a , Luis Valladares c , Marı ´a Luisa Forcelledo a , Luis Constandil a , Guillermo J. Valenzuela d a Departamento de Ciencias Fisiolo ´gicas, Facultad de Ciencias Biolo ´gicas, Pontificia Uniersidad Cato ´lica de Chile, Casilla 114 -D, Santiago, Chile b Departamento de Fisiologı ´a, Facultad de Ciencias Pecuarias y Veterinarias, Santiago, Chile c Instituto de Tecnologı ´a de los Alimentos, Uniersidad de Chile, Santiago, Chile d Department of Women’s Health, Arrowhead Regional Medical Center, Colton, CA, USA Abstract During gestation, the perinatal neuroendocrine axis keeps clock time. In primates, the suprachiasmatic nucleus (biological clock in mammals), shows oscillatory function by midgestation. There is evidence in rodents that the mother, during pregnancy, entrains the fetal suprachiasmatic nucleus (SCN) and newborn circadian rhythms. We are investigating the role of maternal melatonin as an entraining signal for the newborn circadian time-keeping system in the Cebus apella (New World non-human primate). Twenty-four hour rhythms of temperature and cortisol are present in the 4 days old C. apella newborn. Preliminary data suggests that inhibition of maternal melatonin by exposing pregnant females to constant light alters these rhythms. We have found binding sites for melatonin and expression of mRNA for Mel 1A receptor in hypothalamus, kidney and testis. These preliminary results suggest that maternal melatonin may play a role in relating the perinatal circadian time-keeping system to environmental signals. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Circadian rhythms; Melatonin; Non-human primate; Fetus; Newborn www.elsevier.com/locate/mce 1. Introduction The circadian time-keeping system allows predictive adaptation of individuals to the reproducible 24-h day/ night alternations of our planet. Specific physiological functions in the individual are distributed in given segments of the 24-h day, creating an internal temporal order. Transient disturbance of such order accounts for the discomfort of jet lag and play a role in the de- creased performance in shift work. A question receiving current attention is the impact of subjecting preterm babies, for extended periods of time, to non circadian environments in intensive care units. The understanding of the development of the circadian time-keeping sys- tem and of its role in fetal and newborn physiology may identify ways to ease life for such babies. Conceptually, the circadian time-keeping system can be described as a biological clock receiving afferent environmental information and sending efferent out- puts that command overt circadian rhythms (Fig. 1). In mammals, the clock is the suprachiasmatic nucleus (SCN), located bilaterally over the optic chiasm in the hypothalamus (reviewed by van Esseveldt et al., 2000). The SCN oscillates with a period close to (circa) 24-h. Afferent environmental information, mainly the light/ dark cycle (L:D), adjusts the period of the SCN oscilla- tion to 24-h and positions the phase of the oscillation in the 24-h. Efferent signals from the SCN impinge upon regulation of physiological functions resulting in en- docrine (cortisol, TSH, gonadotropins, melatonin, etc.), biophysical (temperature) and behavioral (activity/rest, sleep/wake) circadian rhythms. Phase relationship of the different rhythms within an individual determines an internal temporal order. In the last decade there has been a notable advance in the understanding of the * Corresponding author. Tel.: +56-2-686-2872; fax: +56-2-222- 5515. E-mail address: mseron@genes.bio.puc.cl (M. Sero ´ n-Ferre ´). 0303-7207/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0303-7207(01)00682-7