Chronic Stress During Adolescence Blunts the Exercise-Induced Expression of Thyroid Hormone-Target Genes in Metabolically Active Tissues of Male and Female Rats

Voluntary exercise activates HPT axis(1), that contributes to energy mobilization and energy expenditure. Chronic stress in adulthood inhibits HPT response to voluntary wheel running in a sex dependent manner, inhibiting lipolysis of WAT(2). We evaluated the effect of chronic stress during adolescence on HPT axis response to voluntary exercise in adulthood(3), with emphasis on metabolic response in skeletal muscle and WAT. Wistar male and female rats (N=36 per sex) were divided in an undisturbed group (Control, C; n=18) and one chronic variable stress during adolescence group (CVS; n=18) (males: PND 30-70; females: PND 30-60). As adults (males: PND 84; females: PND: 74) rats were divided in: 1) exercise group: rats placed individually in a cage with a running wheel per 14 nights, 2) sedentary group with ad libitum feeding, 3) sedentary pair-fed group offered the same amount of food consumed by the exercised group, and kept in individual cages during 14 nights (6 rats/group). WAT weight was determined at sacrifice, hormones quantified by RIA and ELISA, gene expression by RT-PCR. Exercise-induced loss of fat mass was not detected in CVS rats. Exercise decreased corticosterone levels in C males and females of both treatments, supporting sex difference on HPA axis reprogramming by CVS. HPT axis response to voluntary exercise is attenuated by CVS also in a sex dimorphic manner: CVS decreased Trh expression in hypothalamic paraventricular nucleus and no changes in thyroid hormones concentration in males, whereas in females, slightly increased TSH, T4 and T3 levels. Sex also influenced the response of skeletal muscle and WAT to CVS. Dio2 and Pgc1a slightly increased expression in skeletal muscle of males, not of females. Adrb3 expression in WAT increased in females, but not in males; exercise-induced stimulation of Hsl expression was not observed in either sex after CVS. These results suggest that CVS imposed during rat adolescence inhibits the responses to voluntary exercise of HPT axis activity of thyroid hormone-targets in WAT and skeletal muscle in sex dependent manner. These changes could lead to reduced mobilization and the utilization of energy fuels coincident with the fatigue observed after exercise in patients with subclinical or clinical hypothyroidism. (Funded: CONACYT 284883, DGAPA IN213419)(1)Uribe, Endocrinology 155:2020-2030, 2014.(2)Parra, Front Endocrinol 10(418):1-13, 2019.(3)Parra, J Endocr Soc 4(Abstract Supp) Abstract SAT-451, 2020.