Rhythms Within Rhythms: The Importance of Oscillations for Glucocorticoid Hormones

Abstract

The circadian activity of the hypothalamic-pituitary-adrenal (HPA) axis is made up from an underlying oscillatory rhythm of ACTH and glucocorticoid pulses that vary in amplitude but not frequency over the 24 h. This oscillatory activity is not the result of a hypothalamic oscillator but emerges as a natural consequence of the feedforward:feedback interaction between the pituitary corticotropes and the glucocorticoid-secreting cells of the adrenal cortex. This oscillatory activity has resulted in adaptations in the way tissues read their 'digital' ligand signal. The adrenal cortex is relatively insensitive to constant signals of ACTH but responds briskly to the equivalent amount of ACTH administered in a pulsatile manner. Similarly glucocorticoid-responsive tissues such as the brain and the liver are able to read the oscillating signals of cortisol or corticosterone secretion, with differential biochemical and functional responses to different patterns of ligand presentation. During a prolonged acute stress there is a major change in the pituitary-adrenal relationship, with a marked increase in the sensitivity of the adrenal to small changes in ACTH, so that following cardiac surgery small oscillations in ACTH result in massive swings in cortisol. This response appears to be due to a change both in the ACTH signalling pathway and in the endogenous activators and inhibitors of glucocorticoid synthesis.

Circadian clock genes and the transcriptional architecture of the clock mechanism

“…In plants that require light for energy production, it is obvious why there is a metabolic link to the day/night cycle (Greenham & McClung 2015); however, animals have also adapted behavioral changes corresponding with light and temperature cycles to respond to and anticipate energetic demands (Bass & Takahashi 2010). In addition to rhythmicity in sleep/activity cycles, in mammals, there are also many other examples of ~24-h physiological rhythms, including body temperature fluctuations (Buhr et al 2010), circulating hormone levels (Lightman 2016), and metabolism (Green et al 2008).…”

The Times of Our Lives: Interaction Among Different Biological Periodicities

“…These neurons in turn release CRH, which is transported through axonal projections to the median eminence (ME) where it is secreted into the hypothalamic-pituitary portal blood system to stimulate the release of adrenocorticotropic hormone (ACTH) from corticotroph cells in the anterior pituitary into the systemic circulation. This leads to increased secretion of glucocorticoids (cortisol in humans and corticosterone in rodents—both referred as CORT the present manuscript) from adrenal cortex, anticipating the activity phase (Lightman, 2016 ; Figure 1B ). Thus, the HPA axis exhibits both circadian and ultradian rhythms in CORT release.…”

Associação da expressão circadiana do cortisol de enfermeiros segundo trabalho em turnos, estresse ocupacional e fadiga

“…Estudos têm demonstrado que a variação circadiana dos ciclos endógenos, incluindo a secreção de hormônios (como os glicocorticoides), da temperatura corporal e do sono-vigília, é responsável tanto pela manutenção da saúde do indivíduo quanto pelo surgimento de doenças. Exemplos de processos de adoecimento em virtude da dessincronização a longo prazo dos ritmos biológicos incluem aumento da pressão arterial, morte por doença cardiovascular, acidente vascular cerebral durante a madrugada, ritmo anormal do cortisol, desordens do sono, imunossupressão, câncer e algumas doenças psiquiátricas, além do aumento do risco de acidentes no trabalho (COSTA, 1996;THOMAS;HERTZMAN;POWER, 2009;ZEE;BOERSMA;HUT, 2009;NAGAI et al, 2011;BOUDREAU, 2014;LIGHTMAN, 2016;NICOLAIDES et al, 2017).…”

“…Há consenso na literatura quanto aos efeitos deletérios do trabalho em turnos, principalmente o noturno, sobre a saúde dos profissionais de enfermagem, sendo a privação do sono o impacto direto mais negativo (ANJUM et al, 2011;OYAMA;FUKAHORI, 2015;JONES et al, 2015;LIGHTMAN, 2016;JIN;HUR;HONG, 2017 (FLO et al, 2012;ASAOKA et al, 2013). As funções rítmicas afetadas pela dessincronização dos ciclos biológicos em trabalhadores em turnos e noturno são principalmente as do sono, do alerta, do desempenho, metabólicas e hormonais (ARENDT, 2010).…”

“…O cortisol (ou hidrocortisona) é um hormônio glicocorticoide sintetizado a partir do colesterol pelo córtex da suprarrenal, sendo o produto final da ativação do eixo HHA (CHROUSOS; GOLD, 2015). Aproximadamente 95% do cortisol sérico encontra-se biologicamente inativo e associado a uma α-proteína denominada transcortina e à albumina, enquanto apenas uma pequena fração (5%) encontra-se livre e biologicamente ativa na circulação, na urina, saliva e nos tecidos (FUKUDA;MORIMOTO, 2001;CHARMANDARI et al, 2003;GOZANSKY, et al, 2005;LIGHTMAN, 2016). Os glicocorticoides agem ligando-se a receptores específicos na cromatina celular, modulando a expressão gênica de maneira hormônio-dependente (MCNALLY et al, 2015).…”