Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

Abstract

Campbell JE, Rakhshani N, Fediuc S, Bruni S, Riddell MC. Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training. J Appl Physiol 106: 66 -72, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.91128.2008.-Although exercise is a common and potent activator of the hypothalamic-pituitary adrenal (HPA) axis, the effects of exercise on the acute stress response are not well understood. Here, we investigated the effects of short-(2 wk) and long-term (8 wk) voluntary wheel running on adrenal sensitivity to ACTH stimulation and the acute stress response to restraint in male rats. Diurnal glucocorticoid patterns were measured on days 7 (all groups) and 35 (8-wk groups). Rats were subjected to 20 min of restraint stress on either week 1 or on week 7 of treatment to assess HPA activation. One week later, exogenous ACTH (75 ng/kg) was administered to assess adrenal sensitivity to ACTH. Following this, adrenals were collected and analyzed for key proteins involved in corticosterone (CORT) synthesis. By the end of week 1, exercising (E) animals had twofold higher peak diurnal CORT levels compared with sedentary (S) animals (P Ͻ 0.01). CORT values were not different between groups at week 8. In response to restraint stress at week 2, CORT values in E were approximately threefold greater than in S (P Ͻ 0.05). No difference was found between E and S rats in the response to, or recovery from, restraint at week 8. During the ACTH challenge at week 2, E demonstrated a ϳ2.5-fold increase in adrenal sensitivity compared with S, while no difference was found between E and S at week 8. The expression of steroidogenic acute regulatory protein was found to be ϳ50% higher in the adrenals in E compared with S at week 2 (P Ͻ 0.05), but no difference existed between groups at week 8. These results show that volitional wheel running initially causes hyperactivation of the HPA axis, due to enhanced adrenal sensitivity to ACTH, but that these alterations in HPA activity are completely restored by 8 wk of training. glucocorticoids; corticosterone; adrenocorticotropic hormone; voluntary exercise; circadian rhythm; restraint stress; adrenocorticotropic hormone challenge; glucocorticoid receptor THE HYPOTHALAMIC-pituitary-adrenal (HPA) axis is a vital component of the body's stress response system. This pathway is activated by a variety of stressors that increase the pituitary release of adrenocorticotropic hormone (ACTH) into the circulation. ACTH stimulates the adrenal release of glucocorticoids (GCs), which, in turn, mobilize energy sources for the increased metabolic demands placed on the body. Acutely, this recruitment of energy sources is essential for events, such as physical exercise; however, restoration of the axis is imperative to prevent overexposure to GCs. It has been well established that chronically elevated levels of plasma GCs can lead to the development of a number of harmful pathologies, including impaired insulin signaling, centr...

Exercise-Associated Changes in the Corticosterone Response to Acute Restraint Stress: Evidence for Increased Adrenal Sensitivity and Reduced Corticosterone Response Duration

“…The HPA-axis response to stressors consists of a sequence of adaptive responses that may have adverse consequences if they are inadequate, or prolonged (Charmandari et al, 2005). Rodents with wheel access typically show a more finely tuned response to stressors, mounting a more robust response than sedentary animals to those with physical components such as forced swim or restraint that would demand sufficient mobilization of energy resources (Campbell et al, 2009;Droste et al, 2007;Droste et al, 2003;Droste et al, 2006), and a more curtailed response to those that are purely psychogenic, such as loud noise or novel cage exposure that would require less energy Droste et al, 2007;Droste et al, 2003). A similar finding is observed in humans in that exercise blunts the HPA-axis response to a single exposure of oral mCPP a 5HT-2C agonist with anxiogenic properties (Broocks et al, 1999;Broocks et al, 2001).…”

“…Wheel running also changes HPA-axis function; for example, wheel running produces elevated CORT at the onset of the diurnal active period in both rats and mice (Adlard and Cotman, 2004;Droste et al, 2003;Fediuc et al, 2006;Stranahan et al, 2006) and is consistently associated with enlarged adrenals Droste et al, 2007;Droste et al, 2003;Droste et al, 2006;Nyhuis et al, 2010;Sasse et al, 2008). The HPA-axis response to both acute (Campbell et al, 2009;Campeau et al, 2010;Droste et al, 2007;Droste et al, 2003;Droste et al, 2006) and repeated Sasse et al, 2008) stress is also altered in wheel-running rodents. Thus, the changes observed in HPA-axis outcomes following wheel running mirror those of chronic stress in some cases (adrenal enlargement, diurnal CORT), and demonstrate stress resistance in others (response to stress).…”

“…Changes in CORT release from the adrenals could result from changes in adrenal sensitivity to adrenocorticotropic hormone (ACTH), or changes in the release of ACTH from the pituitary (Cone et al, 1993). Although several studies have found adrenal enlargement in wheel-running rodents, few studies have directly assessed whether the enlargement leads to increased adrenal sensitivity to ACTH (see Campbell et al, 2009). One mechanism by which termination of CORT release from the adrenals may be achieved is through glucocorticoid receptor (GR)-mediated negative feedback at multiple sites, including the hippocampus and pituitary (Herman et al, 2005).…”

Exercise maintains euglycemia in association with decreased activation of c-Jun NH2-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats

“…6). It may be that the overall distance run by these animals [ϳ5 km/day compared with 10 -15 km/day for healthy rodents (16,29)] and the variability in animals for these parameters prevent us from observing these expected adaptations.…”

Adipogenic and lipolytic effects of chronic glucocorticoid exposure

“…Moreover, enhanced glucocorticoid activity in adipose tissue through increased adipose expression of the glucocorticoidactivating enzyme, 11␤-hydroxysteroid dehydrogenase type 1 (11␤HSD1), results in marked central obesity (19), perhaps through increased rates of adipogenesis (18). In contrast to these findings, we recently demonstrated that increased glucocorticoid exposure, through elevated 11␤HSD1 gene expression and activity specifically in the visceral adipose tissue of exercise-trained rodents, was associated with elevations in lipolysis and markedly diminished visceral adiposity (6,7). This discrepancy between glucocorticoid levels and adiposity makes it difficult to draw generalized conclusions regarding the significance of the lipolytic and antilipolytic actions of these hormones.…”