Environmental control of biological rhythms: effects on development, fertility and metabolism

Internal temporal organisation properly synchronised to the environment is crucial for health maintenance. This organisation is provided at the cellular level by the molecular clock, a macromolecular transcription-based oscillator formed by the clock and the clock-controlled genes that is present in both central and peripheral tissues. In mammals, melanopsin in light-sensitive retinal ganglion cells plays a considerable role in the synchronisation of the circadian timing system to the daily light/dark cycle. Melatonin, a hormone synthesised in the pineal gland exclusively at night and an output of the central clock, has a fundamental role in regulating/timing several physiological functions, including glucose homeostasis, insulin secretion and energy metabolism. As such, metabolism is severely impaired after a reduction in melatonin production. Furthermore, light pollution during the night and shift work schedules can abrogate melatonin synthesis and impair homeostasis. Chronodisruption during pregnancy has deleterious effects on the health of progeny, including metabolic, cardiovascular and cognitive dysfunction. Developmental programming by steroids or steroid-mimetic compounds also produces internal circadian disorganisation that may be a significant factor in the aetiology of fertility disorders such as polycystic ovary syndrome. Thus, both early and late in life, pernicious alterations of the endogenous temporal order by environmental factors can disrupt the homeostatic function of the circadian timing system, leading to pathophysiology and/or disease.This work was supported by grants 1110220 from FONDECYT and ACT1116 from CONICYT, Chile (to HGR); Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Tecnológico e Científico (CNPq; Brazil, to AMC, FGA and JCN); Pro-Reitoria de Pesquisa Universidade Federal de Minas Gerais, Brazil (to MOP); fellowship 21120472 from CONICYT (Chile) to (NM) and an NIEHS sponsored Pilot Grant from the Department of Environmental Medicine at the University of Rochester School of Medicine to MTS

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Clocks underneath: the role of peripheral clocks in the timing of female reproductive physiology

The central circadian pacemaker in the suprachiasmatic nucleus (SCN) is a critical component of the neuroendocrine circuit controlling gonadotropin secretion from the pituitary gland. The SCN conveys photic information to hypothalamic targets including the gonadotropin releasing hormone (GnRH) neurons. Many of these target cells are also cell autonomous clocks. It has been suggested that, rather then being singularly driven by the SCN, the timing of gonadotropin secretion depends on the activity of multiple hypothalamic oscillators. While this view provides a novel twist to an old story, it does little to diminish the central role of rhythmic hypothalamic output in this system. It is now clear that the pituitary, ovary, uterus and oviduct have functional molecular clocks. Evidence supports the notion that the clocks in these tissues contribute to the timing of events in reproductive physiology. The goal of this review is to highlight the current evidence for molecular clock function in the peripheral components of the female hypothalamo-pituitary-gonadal (HPG) axis as it relates to the timing of gonadotropin secretion, ovulation and parturition

Fluorescence/luminescence circadian imaging of complex tissues at single-cell resolution

The use of luciferase reporter genes together with luminescence detection has enabled high frequency monitoring of molecular circadian clock function in living tissues. With the help of an intensified CCD camera combined with an inverted epifluorescence microscope, the authors have established a new imaging strategy that makes use of transgenic cell type-specific expression of fluorescent proteins to identify cells of interest for subsequent circadian luminescence recording at single-cell resolution

Printed in U.S.A. Copyright © 2004 by The Endocrine Society doi: 10.1210/en.2003-1710 Rhythmic Secretion of Prolactin in Rats: Action of Oxytocin Coordinated by Vasoactive Intestinal Polypeptide of Suprachiasmatic Nucleus Origin

Prolactin (PRL) is secreted from lactotrophs of the anterior pituitary gland of rats in a unique pattern in response to uterine cervical stimulation (CS) during mating. Surges of PRL secretion occur in response to relief from hypothalamic dopaminergic inhibition and stimulation by hypothalamic releasing neurohormones. In this study, we characterized the role of oxytocin (OT) in this system and the involvement of vasoactive intestinal polypeptide (VIP) from the suprachiasmatic nucleus (SCN) in controlling OT and PRL secretion of CS rats. The effect of OT on PRL secretion was demonstrated in cultured lactotrophs showing simultaneous enhanced secretion rate and increased intracellular Ca 2 �. Neurosecretory OT cells of the hypothalamic paraventricular nucleus that express VIP receptors were identified by using immunocyto-PROLACTIN (PRL) is one of the most versatile hormone