Neuroendocrine effects of exogenous adropin administration on the hypothalamic pituitary testicular axis in male rats.

Background/aim: Obesity impairs male fertility through metabolic dysfunction, oxidative stress, and disruption of the hypothalamic-pituitary-testicular (HPT) axis. Adropin (ADR), a peptide hormone whose circulating levels are reduced in obesity, plays emerging roles in metabolic homeostasis; however, its involvement in reproductive endocrine regulation remains unclear. The present study was conducted in healthy, nonobese male rats and aimed to investigate the neuroendocrine and testicular effects of exogenous ADR administration, focusing on circulating reproductive hormones, hypothalamic regulatory peptides, and testicular antioxidant pathways. Materials and methods: Thirty-two male Wistar rats were randomized into control, sham, low-dose ADR (4 μg/kg/day), and high-dose ADR (40 μg/kg/day) groups and treated for 10 days. An enzyme-linked immunosorbent assay (ELISA) was used to measure circulating gonadotropins, testosterone, inhibin B, and activin A. Hypothalamic gonadotropin-releasing hormone (GnRH) and kisspeptin expression, and testicular superoxide dismutase 1 (SOD1) localization were assessed by immunohistochemistry. Brain and testis morphology were examined histologically. Results: High-dose ADR administration was associated with increased hypothalamic GnRH and kisspeptin expression, accompanied by reduced circulating LH levels, while FSH concentrations remained unchanged. Testosterone and inhibin B levels were higher, whereas activin A levels were lower, in the high-dose ADR group compared with controls. ADR administration was also associated with enhanced testicular SOD1 immunoreactivity and dose-dependent reductions in body weight. No overt histopathological alterations were observed in the cerebral cortex or testicular tissue. Conclusion: In healthy, nonobese male rats, exogenous ADR administration was associated with changes in central neuroendocrine markers and testicular antioxidant responses without overt histopathological alterations. These findings do not demonstrate improvements in fertility but suggest that ADR may be involved in pathways linking metabolic signals with reproductive endocrine regulation. The potential relevance of these observations to obesity-associated male reproductive dysfunction remains hypothesis-generating and requires confirmation in appropriate disease models and functional reproductive studies.