Endurance treadmill training in rats alters CRH activity in the hypothalamic paraventricular nucleus at rest and during acute running according to its period
Introduction
Acute exercise activates the hypothalamic-pituitary-adrenal (HPA) axis depending on the intensity (Soya, 2001). During intense exercise training, chronic HPA activation such as elevated resting glucocorticoid levels in runners (Luger et al., 1987), cyclists (Silverman and Mazzeo, 1996), and rowers (Snegovskaya and Viru, 1993) is induced and the HPA activation to the same intensity of the acute exercise challenge is reduced (Buono et al., 1987, Luger et al., 1987, White-Welkley et al., 1995). In a previous study, Luger et al. (Luger et al., 1987) inferred that an elevated resting ACTH and glucocorticoid level during intense training may be involved in the hypersecretion of the corticotropin-releasing hormone (CRH) in the hypothalamus. Indeed, the chronic increase in hypothalamic CRH content by running training has been reported in rats (Chennaoui et al., 2002). However, the hypothalamus includes several CRH-containing nuclei (Owens and Nemeroff, 1991) and thus whether CRH synthetic activity increases in the hypothalamic paraventricular nucleus (PVN) is unclear, a predominant region for pituitary-adrenal activation (Bruhn et al., 1984), during exercise training. Although CRH activation of the PVN with the acute running challenge has been reported in previous studies (Richard et al., 1996, Timofeeva et al., 2003), how that effect is modified by running training is currently unknown. Also hypothalamic arginine vasopressin (AVP) is colocalized with the CRH in the PVN (Whitnall et al., 1985) and is presumed to be a factor inducing chronic HPA activation during intense exercise training (Keizer, 1998), though its activity during running training is currently unknown.
We aimed to investigate whether running training would lead to adaptive changes in CRH and/or AVP activity in the parvocellular region of the PVN in the resting condition and responsiveness to an acute running challenge. We report here that running training results in the up-regulated resting CRH mRNA expression and down-regulated running-induced acute response in CRH mRNA when training was done for 4 weeks, where acute running-induced lactate/ACTH responses reduce and pituitary-adrenal activity increase in the resting condition just before running.
Section snippets
Animals
Male Wistar rats aged 4, 6, and 7 weeks were purchased from SLC (Hamamatsu, Japan). The rats were kept in the animal room for 1 week before the experiment. All rats were housed 3 or 4 per cage in a room with a controlled temperature (22 ± 2 °C), humidity (60 ± 10%), and light cycle (lights on from 7:00 A.M. until 7:00 P.M.). Food and water was available ad libitum. The University of Tsukuba's Experimental Animal Use Committee approved the following protocol.
Experimental procedure
As summarized in Fig. 1, rats aged 5,
Results
As shown in Table 1, the relative adrenal weight (mg/100 g body weight) significantly increased with all training independent of the regime length, while the relative thymus weight (mg/100 g body weight) significantly decreased in rats that trained for 2 and 4 weeks, compared with the naive control group.
ANOVA showed significant acute running by training interaction effect on the lactate, glucose, ACTH, and corticosterone levels (Fig. 3). Acute running at 25 meters/minutes for 60 minutes in
Discussion
We aimed at examining whether running training would induce adaptive changes in the CRH and AVP activities in the parvocellular region of the PVN and whether they vary according to the length of the training regime. The results show that running training results in up-regulated resting CRH mRNA in the PVN and down-regulated running-induced acute response in the CRH mRNA with the regime lasting for 4 weeks, with peaked adaptive changes in acute running-induced lactate/ACTH releases (lowered) and
Acknowledgements
We would like to thank Dr. Shinji Nakase (Matsusaka City Hospital), Dr. Masatoshi Takita (National Institute of Advanced Industrial Science and Technology) and our colleagues at the University of Tsukuba's Soya Laboratory, for their kind technical assistance and helpful advice.
References (41)
- et al.
Dynamics of the regulation of the hypothalamo-aituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses
Frontiers in Neuroendocrinology
(1996) - et al.
Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness
Frontiers in Neuroendocrinology
(2003) - et al.
Comparison of selective and complete inhibitors of enkephalin-degrading enzymes on morphine withdrawal syndrome
European Journal of Pharmacology
(1989) - et al.
Treadmill exercise training and estradiol differentially modulate hypothalamic-pituitary-adrenal cortical responses to acute running and immobilization
Physiology and Behavior
(1995) - et al.
Stressinduced increase in vasopressin and corticotropin-releasing factor expression in hypophysiotrophic paraventricular neurons
Endocrinology
(1993) - et al.
Effect of paraventricular lesions on corticotropin-releasing factor (CRF)-like immunoreactivity in the stalk-median eminence: studies on the adrenocorticotropin response to ether stress and exogenous CRF
Endocrinology
(1984) - et al.
Effect of aerobic training on the plasma ACTH response to exercise
Journal of Applied Physiology
(1987) - et al.
Effect of chronic exercise on adrenocortical function and structure in the rat
Journal of Applied Physiology
(1971) - et al.
Effects of moderate and intensive training on the hypothalamo-pituitary-adrenal axis in rats
Acta Physiologica Scandinavica
(2002) - et al.
Chronic stress enhances vasopressin but not corticotropin-releasing factor secretion during hypoglycemia
American Journal of Physiology
(1992)
Effects of long-term voluntary exercise on the mouse hypothalamic-pituitaryadrenocortical axis
Endocrinology
Brain norepinephrine and metabolites after treadmill training and wheel running in rats
Medicine and Science in Sports and Exercise
Exercise physiology: humoral function
Sport Science Review
Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level
Neuroendocrinology
Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity
Acta Physiologica Scandinavica
Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm
Neuroendocrinology
Adaptations of skeletal muscle to endurance exercise and their metabolic consequences
Journal of Applied Physiology
Differential Regulation of Corticotropin-Releasing Hormone and Vasopressin Gene Transcription in the Hypothalamus by Norepinephrine
Journal of Neuroscience
Neurondocrine aspects of overtraining
Overtraining in elite athletes. Review and directions for the future
Sports Medicine
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