Pubertal Triptorelin Exposure Alters Hypothalamic Reproductive–Metabolic Integration in a Sex-Specific Manner
Triptorelin treatment during puberty leads to reproductive suppression and distinct metabolic changes in male and female rats, indicating broader neuroendocrine effects beyond reproductive maturation.
Where it sits
this study against the rest of the triptorelin corpusSummary and findings
This study examined the effects of triptorelin on reproductive and metabolic integration in male and female Wistar rats. The rats received a depot triptorelin injection at pubertal onset, and various physiological parameters were monitored over 28 days. Results indicated significant reproductive suppression and sex-specific metabolic responses.
Abstract
Gonadotropin-releasing hormone agonists are used to treat central precocious puberty and are increasingly prescribed in gender-affirming care. Despite well-established reproductive effects, their broader physiological effects during puberty remain poorly understood. Male and female Wistar rats received a depot triptorelin injection at pubertal onset. Body mass, food intake, and locomotor activity were monitored. After 28 days, reproductive function was assessed, and pituitary and hypothalamic gene expression was analyzed. Changes in gonadal weight, estrous cycle, folliculogenesis, seminiferous tubules’ morphology, and sperm count confirmed the suppression of pubertal maturation. Triptorelin downregulated Gnrhr and Lhb, demonstrating suppression of gonadotrope function. Despite comparable reproductive suppression, metabolic responses to triptorelin were strongly sex-dependent. Females exhibited increased body weight gain accompanied by delayed hyperphagia, whereas males showed reduced body weight gain, unchanged food intake, and increased mean locomotor speed. Female-specific transcriptional remodeling was observed in the hypothalamus, characterized by downregulation of Lepr and Npy and upregulation of Sst and Kiss1 expression. Collectively, these findings demonstrate that pubertal triptorelin treatment induces profound reproductive suppression in both sexes while eliciting sex-specific hypothalamic adaptations in pathways regulating energy homeostasis. This suggests that puberty blockers exert broader neuroendocrine effects beyond the suppression of reproductive maturation.