Abstract
In celebration of the 30th volume of Journal of Biological Rhythms, I am delighted to introduce a serialized feature, The Body Clocks Review Series. These reviews on the biology of mammalian “peripheral” tissue and organ clocks are meant to provide a scholarly entry point for the next generation of investigators, investigators from other fields, or even veterans working on the subject. They will be appearing sequentially in consecutive issues—I anticipate 2 or 3 per print issue with an eventual collection of up to 18—over the course of 2015 and into 2016. The initial installments (on ovary and adrenal) are here in this issue, but look out for others as they become available online ahead of print in the OnlineFirst section of the JBR Web site (http://jbr.sagepub.com/).
We’re now comfortable with the idea that the body is actually a warehouse of interacting cellular circadian clocks, as revealed by the rhythmic expression of genes within autoregulatory transcription-translation feedback loops. But already there were glimpses of body clocks well before the discovery of clock genes and decades before the suprachiasmatic nucleus was crowned The Master Clock. Erwin Bünning, one of the founders of modern circadian biology, noted that despite the central control of circadian rhythmicity in vertebrates, physiological rhythms appear to resynchronize with different speeds after a shift in the light-dark cycle; so inspired, he recorded the peristaltic movements of isolated hamster intestine in a tissue bath over 2-3 days (Bünning, 1958). He reported that gut tension expressed a circadian rhythm, with stronger contraction during the projected night, although it is clear from the data (Fig. 1) why the existence of an intestinal clock was not universally accepted at the time.
Motor activity of an isolated intestinal tract at 21 °C (Fig. 1 from Bünning, 1958).
Richard Andrews and G. Edgar Folk, Jr. cultured hamster adrenal glands and measured oxygen consumption and steroid secretion over a few days (Andrews and Folk, 1964). Not only did they present evidence for a circadian metabolic rhythm in culture, with low activity during the projected night (Fig. 2), but they also described that (a) the phase of the rhythm ex vivo was not substantially influenced by varying the time of sacrifice of the donor animals; (b) the period of the rhythm was relatively independent of flask temperature at 15 °C, 25 °C, and 37 °C; and (c) the pattern of the rhythm appeared 12 h out of phase if donor animals were maintained in a reversed light-dark cycle. They argued that these properties of period and phase “appear to fit with the oscillator model of endogenously based rhythmicity” rather than the action of an uncontrolled exogenous timing signal (Andrews and Folk, 1964). And 1 year later, Gerald Tharp and Folk reported a circadian rhythm of heart rate in isolated rat hearts, hypothesizing that “the circadian rhythms of resting heart rate are controlled by a ‘clock’ located within the heart cell” (Tharp and Folk, 1965). Clear confirmation of these conclusions for adrenal and heart took another 40 years, and Professor Folk celebrated his 100th birthday last November.
Oxygen consumption of 3 individual adrenal glands from donor animals maintained in a 12 h:12 h light:dark cycle (lights on at 0800 h), with time of sacrifice at 0200 h (Fig. 1B from Andrews and Folk, 1964).
Body clocks redux! and may we all live to see our data revitalized!