Immunocytochemical demonstration of day/night changes of clock gene protein levels in the murine adrenal gland: differences between melatonin‐proficient (C3H) and melatonin‐deficient (C57BL) mice

Torres-Farfán, Claudia; Serón-Ferré, Marı́a; Dinet, Virginie; Korf, Horst‐Werner

doi:10.1111/j.1600-079x.2005.00279.x

Cited by 61 publications

(54 citation statements)

References 43 publications

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“…In the human, metabolic clearance of cortisol is higher in the early morning than in the evening [de Lacerda et al, 1973;Plat et al, 1999], therefore the circadian changes in plasma cortisol and in the response to ACTH in the capuchin monkey, most likely originate at the adrenal cortex level. The underlying mechanisms helping to explain our results may involve: (i) circadian changes in the activity and/or expression level of steroidogenic enzymes, shown in rhesus monkey (Macaca mulatta) for 17a-hydroxylase-17-20 lyase and cholesterol side chain cleavage [Lemos et al, 2006]; (ii) clock gene expression as shown in mouse and rhesus monkey adult adrenal [Lemos et al, 2006;Oster et al, 2006;Torres-Farfan et al, 2006a] and adult and fetal capuchin monkey adrenal [Torres-Farfan et al, 2006b;Valenzuela et al, 2005]; and/or (iii) circadian changes in adrenal sensitivity to ACTH mediated by adrenal innervation as described in the rat [UlrichLai et al, 2006]. Clearly, it is necessary to dissect how these overlapping mechanisms contribute to circadian adrenal cortex function.…”

Section: Discussionmentioning

confidence: 90%

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

Torres-Farfán

Valenzuela

Ebensperger

et al. 2007

American J Primatol

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We tested the hypothesis that the capuchin monkey adrenal (Cebus apella) gland has oscillatory properties that are independent of adrenocorticotropic hormone (ACTH) by exploring under ACTH suppression by dexamethasone: (i) maintenance of a circadian rhythm of plasma cortisol and (ii) clock time dependency of plasma cortisol response to exogenous ACTH. The capuchin monkey had a clear ACTH and plasma cortisol rhythm. Dexamethasone treatment resulted in low non-rhythmic ACTH levels and decreased cortisol to 1/10 of control values; nevertheless, the circadian rhythm of plasma cortisol persisted. We found that cortisol response to exogenous ACTH was clock time-dependent. The maximal response to ACTH occurred at the acrophase of the cortisol rhythm (0800 h). These results suggest that the capuchin monkey adrenal cortex may possess intrinsic oscillatory properties that participate in the circadian rhythm of adrenal cortisol secretion and in the circadian cortisol response to ACTH.

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Section: Discussionmentioning

confidence: 90%

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

Torres-Farfán

Valenzuela

Ebensperger

et al. 2007

American J Primatol

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“…Thus, in the capuchin, the fetal SCN and the fetal adrenal show circadian oscillation of two clock genes and evidence of oscillatory function downstream of these genes. Recently, several authors reported the oscillatory expression of clock genes in the adrenal gland of adult rodents (Ishida et al, 2005;Watanabe et al, 2006;Torres-Farfan et al, 2006b) and primate (Lemos et al, 2006), providing strong evidence for the presence of a peripheral clock in this tissue. This possibility is highly relevant, in light of evidence supporting a role for plasma glucocorticoids in the entrainment of other oscillators (Balsalobre et al, 2000), as well as in control of metabolic rhythms in other organs such as liver (Oishi et al, 2005) and adipocytes (AlonsoVale et al, 2005).…”

Section: The Circadian System and Circadian Clocks Throughout Developmentioning

confidence: 97%

Circadian clocks during embryonic and fetal development

Serón-Ferré

Valenzuela

Torres-Farfán

2007

Birth Defects Research Pt C

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101

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Circadian rhythmicity is a fundamental characteristic of organisms, which helps ensure that vital functions occur in an appropriate and precise temporal sequence and in accordance with cyclic environmental changes. Living beings are endowed with a system of biological clocks that measure time on a 24-hr basis, termed the circadian timing system. In mammals, the system is organized as a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, commanding peripheral clocks located in almost every tissue of the body. At the cell level, interlocking transcription/translation feedback loops of the genes Bmal-1, Clock, Per1-2, and Cry1-2, named clock genes, and their protein products results in circadian oscillation of clock genes and of genes involved in almost every cellular function. During gestation, the conceptus follows a complex and dynamic program by which it is simultaneously fit to develop and live in a circadian environment provided by its mother and to prepare for the very different environment that it will experience after birth. It has been known for a number of years that the mother tells the fetus the time of day and season of the year, and that the fetus uses this information to set the phase of fetal and neonatal circadian rhythms. There is evidence that the maternal rhythm of melatonin is one of the time signals to the fetus. In the last few years, the study of the development of the circadian system has turned to the investigation of the oscillatory expression of clock genes and their possible role in development, and to answering questions on the organization of the fetal circadian system. Emerging evidence shows that clock genes are expressed in the oocyte and during early and late development in embryo/fetal organs in the rat and in a fetal primate. The data available raise the intriguing possibility that the fetal SCN and fetal tissues may be peripheral clocks commanded by separate maternal signals. The rapid methodological and conceptual advances on chronobiology may help to unravel how the developing embryo and fetus faces time in this plastic period of life.

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“…Ironically, however, BMAL1 protein levels reach a trough when BMAL1 is displaying the greatest transcriptional activity and peak during the transcription inhibition phase in diverse tissues and cells, including the SCN (23,41,43) (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

BMAL1 Shuttling Controls Transactivation and Degradation of the CLOCK/BMAL1 Heterodimer

Kwon

Lee

Chang

et al. 2006

Molecular and Cellular Biology

147

162

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CLOCK and BMAL1 are bHLH-PAS-containing transcription factors that bind to E-box elements and are indispensable for expression of core circadian clock components such as the Per and Cry genes. A key step in expression is the heterodimerization of CLOCK and BMAL1 and their accumulation in the nucleus with an approximately 24-h periodicity. We show here that nucleocytoplasmic shuttling of BMAL1 is essential for transactivation and for degradation of the CLOCK/BMAL1 heterodimer. Using serial deletions and point mutants, we identified a functional nuclear localization signal and Crm1-dependent nuclear export signals in BMAL1. Transient-transfection experiments revealed that heterodimerization of CLOCK and BMAL1 accelerates their turnover, as well as E-box-dependent clock gene transcription. Moreover, in embryonic mouse fibroblasts, robust transcription of Per2 is tightly associated with massive degradation of the CLOCK/BMAL1 heterodimer. CRY proteins suppressed this process during the transcription-negative phase and led to nuclear accumulation of the CLOCK/BMAL1 heterodimer. Thus, these findings suggest that the decrease of BMAL1 abundance during the circadian cycle reflects robust transcriptional activation of clock genes rather than inhibition of BMAL1 synthesis.Almost all organisms from bacteria to mammals have developed circadian physiology and behavior to adapt to the environmental changes created by the rotation of our planet. Such daily rhythms are controlled by genetically determined and self-sustaining circadian clocks that are composed of networks of transcription-translation feedback loops involving sets of clock genes (15,30,37). In mammals, a network of feedback loops functions robustly not only in the master circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus (26), but also in most tissues (including liver, heart, lung, and muscle) and even in immortalized cell lines (1, 50, 51). These widely dispersed circadian systems are primarily synchronized by the SCN to coordinate circadian timing in vivo (29,36).One of the main questions in clock biology is how the timekeeping system is controlled at the molecular level. Intensive studies in the mouse using genetic and molecular approaches have largely clarified the structure of the central feedback loop (3,30). Two bHLH-PAS-containing transcription factors, CLOCK and BMAL1, form heterodimers that bind to E-box enhancer elements in the promoters of target genes driving the transcription of three period genes (Per1, Per2, and Per3) and two cryptochrome genes (Cry1 and Cry2) (11,14,17,18). After the PER and CRY proteins have been translated in the cytoplasm, they form heterocomplexes that translocate into the nucleus and inhibit their own transcription. CRY plays a crucial role in this negative feedback process by interacting directly with the CLOCK/BMAL1 heterodimers (12,22).Analysis of Bmal1 defective mice has revealed the indispensable role of BMAL1 as the mainspring of the molecular clockwork; thus, targeted disruption of Bmal1 results...

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Immunocytochemical demonstration of day/night changes of clock gene protein levels in the murine adrenal gland: differences between melatonin‐proficient (C3H) and melatonin‐deficient (C57BL) mice

Cited by 61 publications

References 43 publications

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

Circadian clocks during embryonic and fetal development

BMAL1 Shuttling Controls Transactivation and Degradation of the CLOCK/BMAL1 Heterodimer

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