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Performing a hepatic timing signal: glucocorticoids induce gper1a and gper1b expression and repress gclock1a and gbmal1a in the liver of goldfish

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Abstract

Glucocorticoids have been recently proposed as input signals of circadian system, although the underlying molecular mechanism remains unclear. This work investigates the role of glucocorticoids as modulators of clock genes expression in the liver of goldfish. In fish maintained under a 12L:12D photoperiod, an intraperitoneal injection at Zeitgeber Time 2 of a glucocorticoid analog, dexamethasone (1 μg/g body weight) induced per1 genes while decreased gbmal1a and gclock1a expression in the liver at 8 h post-injection. A 4-h in vitro exposure of goldfish liver to cortisol (0.1–10 μM) also induced gper1 genes in a concentration-dependent manner. Similarly, the exposure of the goldfish cultured liver to dexamethasone produced a concentration-dependent induction of gper1 genes. Moreover, this glucocorticoid analog led to a decrease in gbmal1a and gclock1a transcripts, while the other clock genes analyzed were unaffected. The induction of gper1a and gper1b by dexamethasone in vitro was observed at short times (2 h), whereas the reductions of gbmal1a and gclock1a transcripts needed longer exposure times (8 h) to the glucocorticoid to be significant. Additionally, a 2-h exposure to dexamethasone in the liver culture was enough to extend the induction of per genes for more than 12 h. Present results indicate that gper1 genes are targets for glucocorticoids in the regulation of goldfish hepatic oscillator, as previously reported in mammals, suggesting a conserved role of glucocorticoids in the functional organization of the peripheral circadian system in vertebrates. The repression of clock1a and bmal1a is not so well established, and suggests that other clock genes could be glucocorticoid targets in the goldfish liver.

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Abbreviations

BMAL:

Brain and muscle ARNT-like 1

CLOCK:

Circadian locomotor output cycles Kaput

CRY:

Cryptochrome

DEX:

Dexamethasone

DMEM:

Dulbecco’s modified eagle medium

GRE:

Glucocorticoids response element

IP:

Intraperitoneal

PER:

Period

ROR:

Retinoic acid related orphan receptor

RT-qPCR:

Real-time quantitative polymerase chain reaction

SCN:

Suprachiasmatic nucleus

SNK:

Student Newman Keuls

ZT:

Zeitgeber time

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Authors and Affiliations

  1. Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, C/ José Antonio Nováis 12, 28040, Madrid, Spain

    Aída Sánchez-Bretaño, María Callejo, Marta Montero, Ángel L. Alonso-Gómez, María J. Delgado & Esther Isorna

Authors
  1. Aída Sánchez-Bretaño
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  2. María Callejo
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  3. Marta Montero
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  4. Ángel L. Alonso-Gómez
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  5. María J. Delgado
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  6. Esther Isorna
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Corresponding author

Correspondence to Esther Isorna.

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Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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No competing interest declared.

Funding

This research was supported by the Spanish Ministry of Economy and Competitiveness project (MINECO; AGL2013-46448-C3-2-R). A.S-B. was funded by FPI Grant (BES-2011-047620) from MINECO.

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Communicated by G. Heldmaier.

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Sánchez-Bretaño, A., Callejo, M., Montero, M. et al. Performing a hepatic timing signal: glucocorticoids induce gper1a and gper1b expression and repress gclock1a and gbmal1a in the liver of goldfish. J Comp Physiol B 186, 73–82 (2016). https://doi.org/10.1007/s00360-015-0936-2

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  • DOI: https://doi.org/10.1007/s00360-015-0936-2

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