Circadian clocks: regulators of endocrine and metabolic rhythms

Hastings, Michael H.; O’Neill, John S.; Maywood, Elizabeth S.

doi:10.1677/joe-07-0378

Cited by 377 publications

(289 citation statements)

References 106 publications

(82 reference statements)

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“…The circadian system is regulated hierarchically in mammals by the master clock that lies in the suprachiasmatic nuclei (SCN; Hastings et al, 2007). The intrinsic rhythmicity of the SCN is synchronized to the 24-h day by regularly occurring environmental signals or 'Zeitgebers' (Welsh et al, 1995).…”

Section: The Circadian Systemmentioning

confidence: 99%

Does the circadian system regulate lactation?

Plaut

Casey

2012

Animal

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Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/ clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the 'setting' of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition.Keywords: mammary, lactation, circadian rhythm, photoperiod, metabolism ImplicationsThe circadian system coordinates internal physiological processes in mammals and synchronizes these processes to the animal's environment. We review the literature and discuss recent findings from our laboratory and others that suggest the circadian system regulates lactation, including coordinating changes in the dam's physiology needed to initiate and maintain lactation and mediating the photoperiod effect on milk production. Identification of environmental and physiological inputs that affect genes that control circadian rhythms will enable development of approaches to alter gene expression to maximize production efficiency in farm animals. IntroductionNearly all physiological and behavioral functions of animals are rhythmic including secretion patterns of hormones, sleep-wake cycle, metabolism and core body temperature.A circadian rhythm is a roughly 24-h cycle in the biochemical, physiological or behaviora...

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Section: The Circadian Systemmentioning

confidence: 99%

Does the circadian system regulate lactation?

Plaut

Casey

2012

Animal

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“…The resultant fall in the expression of PER and CRY removes their negative feedback and the cycle is reinitiated. An accessory loop involves two transcription factors, Rev-erba and Rora, which have opposite effects on Bmal1 transcription (inhibitory and stimulatory respectively) (Hastings et al 2007).…”

Section: Introductionmentioning

confidence: 99%

“…The circadian rhythm of circulating glucocorticoids (generated via the HPA axis) provides a key coordination link between the central SCN clock and these peripheral clocks (Hastings et al 2007), and as such plays a crucial role in overall metabolic homeostasis. Accordingly, changes in clock gene networks likely mediate maternal physiological adaptations to pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

Wharfe¹,

Mark²,

Wyrwoll³

et al. 2015

Journal of Endocrinology

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Maternal physiological adaptations, such as changes to the hypothalamic-pituitary-adrenal (HPA) axis, are central to pregnancy success. Circadian variation of the HPA axis is dependent on clock gene rhythms in the hypothalamus, but it is not known whether pregnancy-induced changes in maternal glucocorticoid levels are mediated via this central clock. We hypothesized that hypothalamic expression of clock genes changes across mouse pregnancy and this is linked to altered HPA activity. The anterior hypothalamus and maternal plasma were collected from C57Bl/6J mice prior to pregnancy and on days 6, 10, 14 and 18 of gestation (termZd19), across a 24-h period (0800, 1200, 1600, 2000, 0000, 0400 h). Hypothalamic expression of clock genes and Crh was determined by qPCR, plasma ACTH concentration measured by Milliplex assay and plasma corticosterone concentration by LC-MS/MS. Expression of all clock genes varied markedly across gestation, most notably at mid-gestation when levels of each gene were elevated. The pregnancy-induced increase in maternal corticosterone levels (by up to 14-fold on day 14) was not accompanied by a parallel shift in plasma ACTH (28% lower on day 14 compared with non-pregnant levels). Moreover, while circadian rhythmicity in corticosterone was maintained up to day 14 of gestation, this was effectively lost by day 18. Overall, our data show that the central circadian clock undergoes marked adaptations throughout mouse pregnancy, changes that are likely to contribute to maternal physiological adaptations. Importantly, however, neither hypothalamic clock genes nor plasma ACTH levels appear to drive the marked increase in maternal corticosterone after mid-gestation.

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“…Central to the circadian system is a master clock, located in the suprachiasmatic nuclei that underlie entrainment to light (Ralph et al, 1990;Meijer and Schwartz, 2003;Hastings et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The Cerebellum Harbors a Circadian Oscillator Involved in Food Anticipation

Mendoza¹,

Pévet²,

et al. 2010

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The cerebellum participates in motor coordination as well as in numerous cerebral processes, including temporal discrimination. Animals can predict daily timing of food availability, as manifested by food-anticipatory activity under restricted feeding. By studying ex vivo clock gene expression by in situ hybridization and recording in vitro Per1-luciferase bioluminescence, we report that the cerebellum contains a circadian oscillator sensitive to feeding cues (i.e., whose clock gene oscillations are shifted in response to restricted feeding). Food-anticipatory activity was markedly reduced in mice injected intracerebroventricularly with an immunotoxin that depletes Purkinje cells (i.e., OX7-saporin). Mice bearing the hotfoot mutation (i.e., Grid2 ho/ho ) have impaired cerebellar circuitry and mild ataxic phenotype. Grid2 ho/ho mice fed ad libitum showed regular behavioral rhythms and day-night variations of clock gene expression in the hypothalamus and cerebellum. When challenged with restricted feeding, however, Grid2 ho/ho mice did not show any food-anticipatory rhythms, nor timed feeding-induced changes in cerebellar clock gene expression. In hypothalamic arcuate and dorsomedial nuclei, however, shifts in Per1 expression in response to restricted feeding were similar in cerebellar mutant and wild-type mice. Furthermore, plasma corticosterone and metabolites before mealtime did not differ between cerebellar mutant and wild-type mice. Together, these data define a role for the cerebellum in the circadian timing network and indicate that the cerebellar oscillator is required for anticipation of mealtime.

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Circadian clocks: regulators of endocrine and metabolic rhythms

Cited by 377 publications

References 106 publications

Does the circadian system regulate lactation?

Does the circadian system regulate lactation?

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

The Cerebellum Harbors a Circadian Oscillator Involved in Food Anticipation

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