ReviewLight at night as an environmental endocrine disruptor
Introduction
Industrialization and urbanization have been beneficial for the prosperity and health of people, but have also introduced novel threats to wildlife and humans. Environmental endocrine disruptors (EEDs), which alter hormone homeostasis often to the detriment of organisms, are one consequence of human activity. EEDs are a growing concern over the past ∼ 30 years. Although primary focus has been directed to the effects of chemicals found in plasticizers, pharmaceuticals, and pesticides, non-chemical sources such as light at night (LAN) can also interfere with the endocrine system. Low levels of LAN are nearly ubiquitous in the modern world [1], [2]. Because evolution of life has occurred under dark nights over millions of years, and animals have only been exposed to artificial LAN for about 100 years, it is not surprising to discover that LAN likely perturbs circadian organization.
The daily light-dark cycles produced by the earth's rotation are a central influence over organismal behavior. The most salient cyclic behavior is sleep, but many other behavioral and physiological processes follow a daily cyclic pattern as well. Daylight is essential for regulating daily activity patterns in many animals; some animals are active at night, while it is beneficial to be active during the day for others. In addition, core body temperature also follows a daily rhythm in endotherms [3]. Virtually all life has internalized the environmental light-dark cycles in the form of circadian rhythms. Circadian rhythms are endogenous biological rhythms with periods of about 24 h. Circadian rhythms persist in the absence of environmental cues [4]; however, organisms use environmental cues, such as light, to entrain their circadian rhythms precisely to the 24-hour solar day [5].
Entraining circadian rhythms to the solar day allows individuals to synchronize with environmental conditions and display appropriate behaviors and physiological responses. Endogenous circadian rhythms are present in virtually all living organisms, including bacteria, plants, invertebrates, and vertebrates. Again, light is the most effective entraining agent, or zeitgeber. In many vertebrates, light stimulates intrinsically photosensitive retinal ganglion cells, which depolarize and synapse directly onto neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus. The master biological clock is located within the SCN where approximately 20,000 neurons maintain a transcriptional autoregulatory feedback loop. The molecular mechanism of the circadian clock has been reviewed in detail elsewhere [6]. This autoregulatory loop is the primary mechanism driving circadian rhythms; however, there is increasing evidence of additional processes, including posttranslational modifications [7] and cAMP signaling [8], that are also essential for maintenance. Time-of-day information, based on light intensity, is then relayed from the SCN to other brain regions, as well as to peripheral tissues, stimulating appropriate responses.
In vertebrates, in addition to the molecular clock, circadian rhythmicity is also influenced by the nightly secretion of melatonin from the pineal gland. Light stimulates clock gene transcription in the SCN, which sends GABAergic inhibitory signals through the paraventricular nucleus (PVN) of the hypothalamus. These PVN neurons then send projections through the intermediolateral cell column (IML), which stimulates norepinephrine release from the superior cervical ganglion (SCG). Norepinephrine then activates melatonin synthesis and secretion from the pineal gland [9]. In this way, light has an inhibitory effect on melatonin secretion, and the onset of dark triggers melatonin secretion. Melatonin has a negative feedback effect on clock gene transcription in the SCN, and is important for circadian rhythmicity [10], [11].
The circadian clock directly induces a cyclic hormonal rhythm in endocrine tissues. Human serum cortisol concentrations, and corticosterone in many other vertebrates, fluctuate daily, with the highest concentrations in the early morning, within 30–45 min of waking in diurnal species [12], [13]. Serum thyroid-stimulating hormone (TSH) follows a 24-hour profile, with a maximum between 0200 and 0400 h and a nadir between 1600 and 2000 h [14], [15]. Furthermore, melatonin influences several endocrine pathways, including the stress and reproductive axes [16], and also signals to adipose tissue and influences body weight [17]. Many endocrine tissues are also innately cyclic via endogenous expression of clock genes. Therefore, disrupted circadian rhythms can have broad physiological outcomes through several pathways.
The circadian system is vulnerable to aberrant lighting outside the solar day due to its high sensitivity to light. Exposure to constant bright light can greatly disrupt or completely abolish circadian rhythms [18], but brief durations of bright light, or reduced light levels, are also disruptive. Just a brief pulse of light can transiently induce expression of Period 1 (Per1), a core clock gene, and phase shift the molecular clock [19]. In Siberian hamsters, just one 30 min pulse of light during the dark phase was sufficient to activate the neurons of the SCN [20]. Furthermore, very low levels of LAN are also capable of disrupting the clock. The rhythmic expression of three essential clock genes, Per1, Per2, and cryptochrome 2 (Cry2) were attenuated by exposure to just 5 lx of light [21], a level ubiquitous in urban/suburban areas. In addition, light differentially affects secretion of melatonin as a function of the time of day. In humans, peak melatonin secretion occurs between midnight and 0400 h, and exposure to light at night during this time inhibits melatonin secretion for the entire night [22], [23]. Light at night, therefore, can be disruptive at multiple levels of circadian circuitry.
Whereas bright levels of light at night are experienced occasionally, low levels of light at night are fairly ubiquitous. Forty lux of light is the approximate level of light commonly emitted from electronic devices including cellular phones held approximately 30 cm from the face, and therefore is a common exposure level for humans. Five lux of light is approximately 5 times brighter than moonlight and is comparable to levels of light pollution around urban centers [2]; thus, 5 or more lux is a common level of exposure for humans and many other animals (Fig. 1). Light can directly alter endocrine signaling from circadian dysregulation or disrupted or dampened melatonin production, or indirectly through inflammatory responses or elevated circulating stress hormones. We will discuss these mechanisms in relation to the consequences of LAN exposure below.
This review will describe many epidemiological and basic science studies investigating the role of LAN in circadian disruption and physiological outcomes. Epidemiological and clinical results refer to diurnal humans, whereas most basic science research is conducted in nocturnal rodents. Diurnal (day-active) and nocturnal (night-active) species' locomotor activity profiles are opposite from one another, however, the underlying mechanisms of the molecular clock are highly conserved between diurnal and nocturnal species. The structural and molecular components of the SCN are similar; however, some downstream components of the system can vary between nocturnal and diurnal animals [24]. Importantly, the effects of light on entraining circadian rhythms, as well as the photic inhibition of melatonin, are highly similar between nocturnal and diurnal animals. In addition, many of the behavioral effects of circadian dysregulation are similar between diurnal and nocturnal rodents [25], [26]. LAN often disrupts sleep in diurnal animals, and thus the resulting effects cannot be attributed to circadian dysregulation independently from sleep disturbances. Therefore, using nocturnal animals in studies of LAN allows the isolation of the effects of circadian dysregulation in the absence of alterations in sleep.
Section snippets
Effects of light at night on human health
The broad endocrine effects that result from LAN exposure can have many physiological outcomes to human health. Most studies investigate the effects of LAN on disruption of metabolic processes, resulting in obesity or diabetes, and cancer incidence. Additionally, altered hormonal signaling from LAN can result in elevated stress and reproductive abnormalities. In this section we will discuss each of these physiological outcomes in relation to human health.
Agricultural implications of light at night
It is important recognize that although humans are the source of LAN, we are not the only recipients of its effects. Agricultural animals are often housed in rural settings, but the pervasiveness of light pollution does not exclude them from LAN exposure. Perhaps fertility could be improved in livestock and fisheries if dark nights are assured. Conversely, because data indicate LAN can induce an obese phenotype, exposure might assist in increasing the size of livestock animals via metabolic
Ecological consequences of light at night
Many wildlife populations tend to be away from urban centers. However, as made clear by the singing birds in the morning and the deer crossing signs on the highway, wildlife is also pervasive in urban/suburban settings, and therefore is also vulnerable to the effects of artificial lighting. Indeed, several studies indicate artificial LAN alters behavior and physiology in wild species. In great tits (Parus major), there is a strong dose-dependent effect of LAN, in which the onset of activity was
Conclusions
We reviewed the evidence of endocrine disruption via exposure to LAN in human health, agriculture, and wildlife (Fig. 2). The full spectrum of effects is still to be determined, but the consequences are increasingly apparent. Data on the effects of LAN on human health are on the rise, and can likely be applied in agricultural practices as well. Wildlife is not excluded from deleterious effects, and exposure to LAN likely provokes a fitness cost. Therefore, LAN should be considered in urban
Acknowledgements
This review was supported by the National Institutes of Health [R21CA202745 and R01NS092388].
Conflicts of interest
None.
References (128)
- et al.
Molecular architecture of the mammalian circadian clock
Trends Cell Biol.
(2014) - et al.
The diurnal patterns of the adrenal steroids cortisol and dehydroepiandrosterone (DHEA) in relation to awakening
Psychoneuroendocrinology
(2005) - et al.
Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript
Cell
(1997) - et al.
Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: health impacts and mechanisms of circadian disruption
Life Sci.
(2017) - et al.
Dim light at night provokes depression-like behaviors and reduces CA1 dendritic spine density in female hamsters
Psychoneuroendocrinology
(2011) - et al.
Influence of light at night on murine anxiety- and depressive-like responses
Behav. Brain Res.
(2009) - et al.
Melatonin reduces body weight gain and increases nocturnal activity in male Wistar rats
Physiol. Behav.
(2013) - et al.
Hypothalamic orexin neurons regulate arousal according to energy balance in mice
Neuron
(2003) - et al.
Individual differences in wheel-running rhythms are related to temporal and spatial patterns of activation of orexin A and B cells in a diurnal rodent (Arvicanthis niloticus)
Neuroscience
(2004) - et al.
Night work and breast cancer risk: a systematic review and meta-analysis
Eur. J. Cancer
(2005)
Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies
Cancer Epidemiol.
Role of the pineal gland in aetiology and treatment of breast cancer
Lancet
Melatonin's growth-inhibitory effect on hepatoma AH 130 in the rat
Cancer Lett.
Mice exposed to dim light at night exaggerate inflammatory responses to lipopolysaccharide
Brain Behav. Immun.
New insights into role of microenvironment in multiple myeloma
Lancet
The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo
Cell
The circadian gene Per1 plays an important role in cell growth and DNA damage control in human cancer cells
Mol. Cell
Melatonin biosynthesizing enzyme genes and clock genes in ovary and whole brain of zebrafish (Danio rerio): differential expression and a possible interplay
Gen. Comp. Endocrinol.
The first world atlas of artificial night sky brightness
Mon. Not. R. Astron. Soc.
The new world atlas of artificial night sky brightness
Sci. Adv.
Temperature as a universal resetting cue for mammalian circadian oscillators
Science
Rhythm of the rectal temperature during a 6-month free-running experiment
J. Appl. Physiol.
Influence of light on circadian rhythmicity in humans
Post-translational modifications regulate the ticking of the circadian clock
Nat. Rev. Mol. Cell Biol.
cAMP-dependent signaling as a core component of the mammalian circadian pacemaker
Science
Suprachiasmatic nucleus and melatonin: reciprocal interactions and clinical correlations
Neurology
Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus
Fed. Proc.
Melatonin
Clin. Endocrinol.
Experimental alteration of the circadian rhythm in plasma cortisol (17-OHCS) concentration in man
J. Clin. Endocrinol. Metab.
Serum thyrotropin (TSH) in pituitary and/or hypothalamic hypothyroidism: normal or elevated basal levels and paradoxical responses to thyrotropin-releasing hormone
J. Clin. Endocrinol. Metab.
Free triiodothyronine has a distinct circadian rhythm that is delayed but parallels thyrotropin levels
J. Clin. Endocrionol. Metab.
Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate
J. Pineal Res.
Melatonin promotes circadian rhythm-induced proliferation through Clock/histone deacetylase 3/c-Myc interaction in mouse adipose tissue
J. Pineal Res.
Conditioned stimulus control in the circadian system: two tales tell one story
J. Biol. Rhythm.
Nocturnal light exposure impairs affective responses in a wavelength-dependent manner
J. Neurosci.
Dim light at night disrupts molecular circadian rhythms and increases body weight
J. Biol. Rhythm.
Age- and mental health-related circadian rhythms of plasma levels of melatonin, prolactin, luteinizing hormone and follicle-stimulating hormone in man
J. Endocrinol.
Minireview: entrainment of the suprachiasmatic clockwork in diurnal and nocturnal mammals
Endocrinology
Dim nighttime light impairs cognition and provokes depressive-like responses in a diurnal rodent
J. Biol. Rhythm.
Prevalence of childhood and adult obesity in the United States, 2011–2012
JAMA
Annual medical spending attributable to obesity: payer- and service-specific estimates
Health Aff.
Effect of shift work on body mass index: results of a study performed in 319 glucose-tolerant men working in a southern Italian industry
Int. J. Obes. Relat. Metab. Disord.
Impact of circadian misalignment on energy metabolism during simulated nightshift work
PNAS
Night shift work and incidence of diabetes in the Danish nurse cohort
Occup. Environ. Med.
Does artificial light-at-night exposure contribute to the worldwide obesity pandemic?
Int. J. Obes.
Mismatch of sleep and work timing and risk of type 2 diabetes
Diabetes Care
Glucose tolerance in mice exposed to light-dark stimulus patterns mirroring dayshift and rotating shift schedules
Sci Rep
Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats
Diabetologia
Light at night increases body mass by shifting the time of food intake
PNAS
Acute dim light at night increases body mass, alters metabolism, and shifts core body temperature circadian rhythms
Chronobiol. Int.
Cited by (119)
Pressures of the urban environment on the endocrine system: Adverse effects and adaptation
2024, Molecular and Cellular EndocrinologyUrban abiotic stressors drive changes in the foraging activity and colony growth of the black garden ant Lasius niger
2024, Science of the Total EnvironmentEffect of light intensity, spectrum, and uniformity on the ability of dairy cows to navigate through an obstacle course
2023, Journal of Dairy ScienceLight pollution: Interests of feline model as a sentinelle
2023, Bulletin de l'Academie Nationale de Medecine