# Long-Term Effects of Stress During Adolescence on the Sex-Dependent Responses of Thyroid Axis and Target Tissues to Exercise in Male and Female Wistar Rats

## TL;DR

Stress during adolescence in rats affects how their thyroid system and body tissues respond to exercise in adulthood, and these effects differ between males and females.

## Contribution

The study reveals sex-specific, long-term effects of adolescent stress on thyroid axis and metabolic responses to exercise in adult rats.

## Key findings

- Chronic adolescent stress increased Gr and Npy expression in specific brain regions of male rats.
- Exercise increased metabolic gene expression in multiple tissues, but these effects were largely repressed in stress-exposed rats.
- Sex differences were observed in thyroid hormone levels and gene expression changes following stress and exercise.

## Abstract

The response of the hypothalamic–pituitary–thyroid (HPT) axis to energy demands is perturbed by previous chronic stress perceived during the neonatal or adult periods. We examined the effects of chronic variable stress (CVS) during adolescence on the responses of the HPT axis and target tissues of adult rats to 14 days of voluntary wheel running (Ex) or pair-feeding (PF) to match the reduced food intake of exercised rats. CVS increased the expression of Gr in the paraventricular nucleus (PVN) and of Npy in the mediobasal hypothalamus (MBH) in males; serum corticosterone concentration increased (1.5×), MBH Dio2 and PVN Trh decreased (40%) in both sexes, serum fT4 increased only in males, while T3 and fT3 increased (2×) in females. Exercise decreased Cort and increased PVN Trh expression only in males. In both sexes, it increased MBH Pomc and Dio2 (2×), skeletal muscle Dio2 and Pgc1a (2×), inguinal and perigonadal white adipose tissue (WAT) Adrb3, Dio2, Pparg, Hsl (1.5×), and brown adipose tissue Adrb3, Dio2, and Ucp1. All exercise-induced changes were repressed in CVS-Ex, except Hsl in inguinal WAT of both sexes, or BAT Dio2 in females, which, in contrast, was stimulated (1.5×). PF had lower values than sedentary in most parameters. These results support the idea that adolescent stress affects adult metabolic and neuroendocrine responses to exercise in a sex-specific manner.