The mammalian circadian timing system is organized into hierarchical structures with a central clock in the suprachiasmatic nucleus (SCN) and subsidiary peripheral oscillators. After the discovery of the local clockwork in peripheral organs and tissues, which have a molecular makeup similar to the central pacemaker SCN, uncovering the roles of the peripheral clock in the rhythmic physiology has been an emerging goal in chronobiology. Glucocorticoid (GC) is a multifunctional adrenal steroid hormone that shows a robust circadian rhythm. The daily GC rhythm has long been thought to be governed by the SCN via the hypothalamus-pituitary-adrenal neuroendocrine axis. Recent findings, however, indicate that multiple regulatory mechanisms, including the adrenal intrinsic mechanism by the peripheral clock, are also involved. GC regulates diverse physiological processes and acts as a signal for resetting peripheral clocks, which suggests the importance of the GC rhythm in harmonizing overall circadian physiology and behavior. Therefore, in this review, we will discuss the important role of the adrenal peripheral clockwork in the circadian regulation of GC and its physiological relevance in the circadian timing system.
"relationship between baseline plasma and feather CORT concentrations (Fig. 2). The weak relationship between baseline plasma CORT and feather CORT may be due to either the relatively weak adrenocortical response of rhinoceros auklet chicks to food stress (Sears and Hatch, 2008) or to a diurnal cycle in baseline CORT secretion (Chung et al., 2011). Furthermore, it is not unusual for baseline plasma CORT to be highly variable, and when sample sizes are relatively small, this variability may decrease the explanatory power of independent variables. "
[Show abstract][Hide abstract] ABSTRACT: In nest-bound avian offspring food shortages typically trigger a release of the stress hormone corticosterone (CORT). Recent studies indicate that CORT is passively deposited in the tissue of growing feathers and thus may provide an integrated measure of stress incurred during development in the nest. The current hypothesis predicts that, assuming a constant rate of feather growth, elevated CORT circulating in the blood corresponds to higher levels of CORT in feather tissue, but experimental evidence for nutritionally stressed chicks is lacking. Here we examine how food limitation affects feather CORT content in the rhinoceros auklet (Cerorhinca moncerata). We i) used captive chicks reared on control vs. restricted diets, and ii) applied this technique to free-living chicks with unknown nutritional histories that fledged at three separate colonies. We found that i) feather growth was not affected by experimentally-induced nutritional stress; ii) captive chicks raised on a restricted diet had higher levels of CORT in their primary feathers; iii) feather CORT deposition is a sensitive method of detecting nutritional stress; and iv) free-living fledglings from the colony with poor reproductive performance had higher CORT in their primary feathers. We conclude that feather CORT is a sensitive integrated measure revealing the temporal dynamics of food limitations experienced by rhinoceros auklet nestlings. The use of feather CORT may be a powerful endocrine tool in ecological and evolutionary studies of bird species with similar preferential allocation of limited resources to feather development.
"At baseline levels, CORT is important in regulating basic metabolism; at higher concentrations, it plays a key role in the vertebrate stress response  . There are predictable changes in CORT titers depending on time of day   and season . There are also less predictable changes in plasma CORT concentrations depending on species, population , and the extent of chronic stress   . "
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoid hormones play a key role in the stress response, but plasma concentrations vary based on physiological, environmental, or social parameters. However, hormone titers alone do not determine organismal response. To enhance our understanding of glucocorticoid actions we can examine 'downstream' factors in the organismal stress response, measuring glucocorticoid receptors across target tissues. Here, we characterized intracellular binding sites for CORT (corticosterone, the avian glucocorticoid) in house sparrow (Passer domesticus) brain, liver, skeletal muscle, spleen, fat, testes, ovary, kidney and skin. We used radioligand binding assays to identify total capacity, relative density and affinity for CORT of intracellular receptors in each tissue. Most evidence supported two binding sites similar to mammalian low-affinity glucocorticoid receptor (GR) and a high-affinity mineralocorticoid receptor (MR) for brain, liver, kidney and testes, and only a GR-like receptor for muscle, spleen, fat, ovary and skin. However, kidney data were somewhat more complicated, possibly hinting at a mineralocorticoid function for CORT and/or GR in birds. In all tissues, GR and MR affinities were close to published house sparrow values (K(d)∼6nM for GR, and ∼0.2nM for MR). Taken together, these data show that CORT receptor distribution appears to be as widespread in birds as it is in mammals, and suggest that independent regulation of peripheral receptors in different target tissues may play a role in CORT's diverse physiological effects.
General and Comparative Endocrinology 08/2012; 179(2):214-20. DOI:10.1016/j.ygcen.2012.08.007 · 2.47 Impact Factor
"They synchronize the circadian cellular clocks in various peripheral tissues   , induce GR interactions with the circadian co-regulators Cry1 and Cry2 , and are also involved in the regulation of the cell cycle and proliferation (reviewed in ). Glucocorticoids are released from the adrenal gland as a result of a dynamic interplay between of the circadian activity of hypothalamicpituitary-adrenal axis and the rhythmicity of the adrenal gland itself, which is regulated by its own circadian clock . Changes in plasma level of the glucocorticoids show a maximum before the beginning of the active phase (day for humans and night for rodents), and then declines to a minimum level in the early resting phase. "
[Show abstract][Hide abstract] ABSTRACT: Transcription is a tightly regulated cellular function which can be triggered by endogenous (intrinsic) or exogenous (extrinsic) signals. The development of novel techniques to examine the dynamic behavior of transcription factors and the analysis of transcriptional activity at the single cell level with increased temporal resolution has revealed unexpected elements of stochasticity and dynamics of this process. Emerging research reveals a complex picture, wherein a wide range of time scales and temporal transcription patterns overlap to generate transcriptional programs. The challenge now is to develop a perspective that can guide us to common underlying mechanisms, and consolidate these findings. Here we review the recent literature on temporal dynamics and stochastic gene regulation patterns governed by intrinsic or extrinsic signals, utilizing the glucocorticoid receptor (GR)-mediated transcriptional model to illustrate commonality of these emerging concepts. This article is part of a Special Issue entitled: Chromatin in time and space.
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