Rasha M. Salama; Asmaa Saeed Essawy & Marwa Abd El Rasoul Omar
Effects of Glucagon-like peptide-1 receptor agonists on the thyroid gland, particularly the parafollicular C-cells, have been noted for injectable formulations, but comprehensive data regarding the novel oral formulation of semaglutide remain limited. The aim of the study was to investigate and quantify the dose-dependent effects of chronic oral semaglutide administration on the endocrine function, morphology, and cellular markers of proliferation and apoptosis in the thyroid gland of male albino rats. Forty (40) adult male rats were divided into 4 groups; control and 3 semaglutide treatment groups (Low-Dose, Medium-Dose, and High-Dose), corresponding to the human therapeutic range of 3 to 14 mg, and treated for 30 days. Endocrine status was assessed via serum levels of tri-iodothyronine (T3(, thyroxine (T4(, and thyroid stimulating hormone (TSH). Histological analysis included Hematoxylin and Eosin (Hx&E) staining, Periodic Acid Schiff (PAS) reaction, and immunohistochemical (IHC) quantification of Ki67, Calcitonin, and BAX. All treated groups exhibited a significant, dose-dependent reduction in body weight. The Medium- Dose and High-Dose groups showed a highly significant decline (P<0.001) in all 3 measured serum thyroid hormones. Pathological examination revealed dose-proportional deterioration, including follicular atrophy and epithelial exfoliation. Immunohistochemistry confirmed a highly significant, dose-dependent increase in calcitonin immunoreactive C- cells numbers and Ki67 and BAX expression in the higher-dose groups (P< 0.001). Oral semaglutide induces notable and dose-dependent detrimental effects on the morphological and endocrine integrity of the rat thyroid gland, particularly at doses equivalent to 7 and 14 mg in humans. This mandates further research to delineate the underlying molecular mechanisms.
KEY WORDS: Semaglutide; TSH; Ki67; Calcitonin; BAX.
SALAMA, R. M.; ESSAWY, A. S. & OMAR, M. A. Eminent effects of glucagon-like peptide-1 receptor agonist on the thyroid gland of male albino rats. Int. J. Morphol., 44(2):542-554, 2026.
