HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Hastings, M. Articles by Maywood, E. S Search for Related Content PubMed PubMed Citation Articles by Hastings, M. Articles by Maywood, E. S

Division of Neurobiology, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK

(Correspondence should be addressed to M Hastings; Email: mha{at}mrc-lmb.cam.ac.uk)

Daily and seasonal rhythms in the endocrine system are co-ordinated by a hypothalamic pacemaker, the suprachiasmatic nuclei (SCN) that is synchronised to solar time by direct retinal afferents. Individual SCN neurons are circadian clocks, their intrinsic oscillator consisting of a series of interlinked autoregulatory transcriptional/post-translational feedback loops incorporating Period (Per) and Cryptochrome (Cry) genes. Mutations that alter the rate of transcription of Per and Cry genes or the stability of Per and Cry proteins affect clock speed. Molecular timekeeping in SCN neurons is synchronised and sustained by interneuronal neuropeptidergic signals. A molecular clock mechanism comparable to that of the SCN is present in most major organ systems. These tissue clocks are synchronised by endocrine, autonomic and behavioural cues that are dependent on the SCN, and in turn they drive the circadian expression of local transcriptomes, thereby co-ordinating circadian metabolism and physiology. Rhythmic glucocorticoid signalling is a prominent mediator of SCN output and internal synchroniser. The role of local SCN-synchronised clocks in controlling vital processes, including xenobiotic detoxification, cell division and nutrient metabolism, is essential to health, and disturbances to circadian timing arising from modern working schedules are becoming recognised as an increasingly relevant factor in major systemic illness. Moreover, the newly identified molecular components of circadian control systems provide novel avenues for therapeutic intervention.

This article has been cited by other articles:

				R. R. Almon, E. Yang, W. Lai, I. P. Androulakis, S. Ghimbovschi, E. P. Hoffman, W. J. Jusko, and D. C. DuBois Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1031 - R1047. [Abstract] [Full Text] [PDF]

				C. W. Wilkinson Circadian Clocks: Showtime for the Adrenal Cortex Endocrinology, April 1, 2008; 149(4): 1451 - 1453. [Full Text] [PDF]

				A.S.I. Loudon, Q.J. Meng, E.S. Maywood, D.A. Bechtold, R.P. Boot-Handford, and M.H. Hastings The Biology of the Circadian Ck1{epsilon} tau Mutation in Mice and Syrian Hamsters: A Tale of Two Species Cold Spring Harb Symp Quant Biol, January 1, 2007; 72(0): 261 - 271. [Abstract] [PDF]