Voluntary Exercise Adapts the Hypothalamus-Pituitary-Thyroid Axis in Male Rats

Abstract

The hypothalamic-pituitary thyroid (HPT) axis modulates energy homeostasis. Its activity decreases in conditions of negative energy balance but the effects of chronic exercise on the axis are controversial and unknown at hypothalamic level. Wistar male rats were exposed for up to 14 days to voluntary wheel running (WR), or pair-feeding (PF; 18% food restriction), or to repeated restraint (RR), a mild stressor. WR and RR diminished food intake; body weight gain decreased in the 3 experimental groups, but WAT mass and serum leptin more intensely in the WR group. WR, but not RR, produced a delayed inhibition of central markers of HPT axis activity. At day 14, in WR rats paraventricular nucleus-pro-TRH mRNA and serum TSH levels decreased, anterior pituitary TRH-receptor 1 mRNA levels increased, but serum thyroid hormone levels were unaltered, which is consistent with decreased secretion of TRH and clearance of thyroid hormones. A similar pattern was observed if WR animals were euthanized during their activity phase. In contrast, in PF animals the profound drop of HPT axis activity included decreased serum T3 levels and hepatic deiodinase 1 activity; these changes were correlated with an intense increase in serum corticosterone levels. WR effects on HPT axis were not associated with changes in the activity of the hypothalamic-pituitary adrenal axis, but correlated positively with serum leptin levels. These data demonstrate that voluntary WR adapts the status of the HPT axis, through pathways that are distinct from those observed during food restriction or repeated stress.

60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

“…However, adipose tissue mass and leptin serum levels were reduced exclusively after exercise; Trh mRNA in the PVN and TSH serum levels diminished, compared to naïve rats, more in the pair-fed than in the exercised group; only pair-fed animals had low T 3 serum levels. The inhibition of the HPT axis caused by diminished food intake was thus partially compensated with exercise and the changes to all the parameters of the HPT axis correlated with distance run and loss of fat mass (Uribe et al 2014). These results suggest that although TH and nutritional status modulate the basal state of the HPT axis, immediate energy demands may override leptin or TH signaling.…”

“…Other examples of HPT axis activation are observed in response to an acute increase in physical activity (Fortunato et al 2008, Gutiérrez-Mariscal et al 2012 or after 2 weeks of voluntary exercise in rats (Uribe et al 2014). Wheel running diminishes food intake by 18% compared to sedentary animals.…”

“…Cold-induced TRH expression is independent of circulating TH concentration (Zoeller et al 1990) or of nutritional status (Jaimes-Hoy et al 2008), but is inhibited by a previous stress exposure (Uribe et al 2011) or corticosterone injection (Sotelo-Rivera et al 2014). Humans exposed to cold for over 60 h activate the HPT axis, which is not inhibited if food intake is reduced .Other examples of HPT axis activation are observed in response to an acute increase in physical activity (Fortunato et al 2008, Gutiérrez-Mariscal et al 2012 or after 2 weeks of voluntary exercise in rats (Uribe et al 2014). Wheel running diminishes food intake by 18% compared to sedentary animals.…”

Regulation of TRH neurons and energy homeostasis-related signals under stress

“…Exercise blunted several of the changes produced by the 18% reduced food intake, i.e. Trh diminished 30% instead of the 50% seen in the pair-fed rats, and neither T 3 or deiodinases activities were altered; however, white adipose tissue (WAT) mass diminished in exercised rats whose serum leptin concentration decreased much more than that of the pair-fed rats; furthermore, the amount of exercise performed correlated positively with T 3 and Trh mRNA levels and negatively with WAT mass (Uribe et al 2014). Exercise thus overrides the signals of energy deficiency, such as low serum leptin concentration; the intermittent activation of PVN-TRH neurons and of TH release (seen after an acute increase in physical activity, see below) may guarantee maintenance of TH levels for adequate fuel supply to oxidizing tissues, such as released fatty acids from WAT (Klieverik et al 2009, Weber 2011.…”

“…Constriction injury of sciatic nerve decreases Trh mRNA levels in the whole hypothalamus as well as serum TH levels (Kilburn-Watt et al 2010). Foot shock (14 sessions/day) decreases total and free T 4 and T 3 serum concentrations without affecting Trh in the PVN, whereas Agrp mRNA levels in the ARC increase (Helmreich et al 2005); a milder form of stress, such as 60 min daily restraint for 2 weeks, does not affect Trh mRNA expression in the PVN nor TSH or TH serum levels (Uribe et al 2014). The intensity of the stressors thus seems to determine HPT activity and Trh expression; however, despite significant changes not being observed in the latter two paradigms, levels of Trh mRNA correlate negatively with those of corticosterone and positively, with body-weight changes.…”