Changes in the Adrenal Cortex Induced by Liraglutide Treatment and Exercise in a Rat Model of Menopausal Transition

The menopausal transition is a key period marked by changes in cardiometabolic health and adrenal function, representing an important window for targeted interventions to improve women's health. Glucagon-like peptide-1 receptor agonists improve metabolic parameters, while physical exercise provides well-established benefits; however, their effects during the menopausal transition remain insufficiently explored. This study examined the effects of liraglutide (0.186 mg/kg; corresponding to the human equivalent dose of 1.8 mg/day used for type 2 diabetes treatment) and exercise on the adrenal gland in a rat model of menopausal transition. Three-month-old females served as young controls (CY), while 16-month-old acyclic females were assigned to control (C), liraglutide (L), exercise (E), or combined treatment (L+E). Compared with CY, the C group showed increased body mass and adrenal alterations, including reduced adrenal weight and volume, cortical atrophy, increased collagen content, decreased STAR, and increased pAMPKα optical density (p ≤ 0.05). Sf1 and Star were upregulated in L, E, and L+E compared with C, most prominently in L (p ≤ 0.05), while Cyp11b2 was increased in L and L+E (p ≤ 0.05). Hormone analysis showed reduced 17β-estradiol, corticosterone, and aldosterone in C compared with CY. Corticosterone was further reduced in L compared with C, while aldosterone increased in L and L+E compared with C (p ≤ 0.05). In conclusion, the menopausal transition induced adrenal morpho-functional remodeling. Liraglutide intervention had the greatest impact on steroidogenic output, both alone and in combination with exercise, while exercise alone showed no significant effect.