Long-Term Effects of Stress During Adolescence on the Sex-Dependent Responses of Thyroid Axis and Target Tissues to Exercise

The response of the hypothalamic-pituitary-thyroid (HPT) to energy demands is perturbed by previous chronic stress perceived during the neonatal or the adult periods, We examined sex-specific effects of chronic variable stress (CVS) during adolescence on the responses of these axes and target peripheral tissues to volun-tary wheel-running (Ex) in adult rats. Two weeks of Ex stimulated mediobasal hypothalamus (MBH)-Pomc expression in both sexes, but this response was blunted by CVS. CVS altered basal HPA activity only of adult males increasing paraventricular nucleus (PVN) Gr and arcuate-Npy expression, and serum Cort levels. Ex reduced serum Cort concentration in controls. CVS decreased MBH-Dio2 and PVN-Trh expression, raising total and free T3 levels in females. In males, CVS reduced MBH-Dio2, -Trhde, and PVN-Trh expression, impairing exercise-induced expression and reducing serum T3/T4 ratio. The exer-cise-induced gene-expression of Dio2 and Pgc1a in skeletal muscle, of Adrb3, Dio2, Pparg, Hsl in inguinal and gonadal white-adipose tissues, and of Adrb3 and Ucp1 brown adipose tissue was blunted by CVS in both sexes except Hsl in in-guinal of both and BAT-Dio2 in brown adipose tissue of females that were not affected by stress. These results support that adolescent stress impacts adult met-abolic and neuroendocrine responses to exercise in a sex-specific manner.