Voluntary Exercise Impacts on the Rat Hypothalamic-Pituitary-Adrenocortical Axis Mainly at the Adrenal Level

Abstract

Introduction: Evidence is accumulating that the regular performance of exercise is beneficial for stress coping. However, the hypothalamic-pituitary-adrenocortical (HPA) axis of voluntarily exercising rats has never been comprehensively investigated. Methods: Therefore, male Sprague-Dawley rats were given access to a running wheel in their home cage for 4 weeks in which they ran 4–7 km per night. Results: After 4 weeks, the exercising animals showed significantly less body weight gain, less abdominal fat tissue, decreased thymus weight, and increased adrenal weight (relative to body weight). Furthermore, tyrosine hydroxylase (TH) mRNA levels were selectively increased in the right adrenal me- dulla indicating an increase in sympathoadrenomedullary capacity in exercising rats. No changes were observed in paraventricular corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) and oxytocin mRNA levels. Mineralocorticoid receptor (MR) mRNA levels in hippocampus and glucocorticoid receptor (GR) mRNA levels in frontal cortex, parvocellular paraventricular nucleus and anterior pituitary were unchanged, whereas GR mRNA levels were increased in distinct hippocampal cell layers. Early morning baseline levels of plasma ACTH and corticosterone were similar in both groups. Interestingly, the response to different stressful stimuli (e.g. forced swimming, novelty) revealed that the exercising rats showed stressor-specific changes in HPA hormone responses. Forced swimming evoked a markedly enhanced response in corticosterone levels in the exercising rats. In contrast, if rats were exposed to a novel environment, exercising rats showed a much lower response in corticosterone than the control animals. However, the response in ACTH to either stressor was comparable between groups. Thus, in exercising rats physically demanding stressors evoke enhanced glucocorticoid responses whereas mild psychologically stressful stimuli such as novelty result in an attenuated glucocorticoid response. Interestingly, this attenuated hormone response corresponded with the observation that the exercising rats showed less anxious behaviour in the novelty situation. Conclusions: The differential responses in plasma corticosterone levels to different types of stress in the face of comparable responses in ACTH levels underscore the existence of critical regulatory control mechanisms at the level of the adrenal gland. We have hypothesized that changes in the sympathoadrenomedullary input may play an important role in these distinct glucocorticoid responses to stress. Our previous studies have shown similar changes in voluntarily exercising mice. Therefore, we conclude that the effects of exercise on the organism are not species-specific. Thus, our observations may have translational implications for the human situation.

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

“…In accordance with this, 2 wk of voluntary wheel running have recently been shown to increase mRNA levels of StAR (25). Alternatively, a recent study has also suggested that enhanced sympathoadrenomedullary activity, found to be associated with exercise training, may positively modulate adrenal sensitivity to ACTH (8). Considering that epinephrine has previously been demonstrated to stimulate adrenocortical steroidogensis and secretion of GCs (8), our study proposes possible target genes on which this increased sympathoadrenomedullary input may be operating.…”

“…This suggests that impaired negative feedback sensitivity is likely not the cause of HPA hyperactivity during the early stages of exercise training. Rather, we and others (8) believe that significant adaptations in the adrenal glands occur with prolonged training, such that adrenal sensitivity to ACTH is enhanced. Indeed, we clearly confirm this hypothesis here, by using a standardized ACTH challenge to show that exercising animals have increased adrenal sensitivity at 2 wk (Fig.…”

“…However, the same group also found no significant changes in hippocampus GR with milder exercise intensities (18). Indeed, neither long-term forced swim training (26) nor voluntary wheel running (8,14) lowers central corticoreceptors in rodents. In fact, Droste et al (8) found that Fig.…”

“…This was one of the first studies to illustrate that volitional exercise may differ from forced exercise in the adaptive responses of the HPA axis. Employing a similar voluntary exercise model, Droste and colleagues (8) recently found that rats, subjected to 4 wk of voluntary wheel running, had similar ACTH levels but higher GC levels during forced swim stress compared with previously sedentary rats. Thus, unlike with forced exercise, voluntary exercise may increase adrenal sensitivity to ACTH.…”

Short-term voluntary exercise in the rat causes bone modeling without initiating a physiological stress response

“…The rat model of exercise has been used extensively to study the physiological effects of physical activity using such exercise modalities as swimming (24, 32), running (20,29,41,49,52), jumping (57), tower climbing (43), rising to an erect bipedal stance (11, 64), and weight lifting (62). The effects of exercise on bone have been widely characterized in the rat.…”