Neurotrophic effects of GH and GnRH in a full sciatic nerve transection model in male rats.

Abstract

Peripheral nerve injuries, such as sciatic nerve transection (SNT), are associated with significant sensory and motor deficits. Growth hormone (GH) and gonadotropin-releasing hormone (GnRH) have been shown to exert neurotrophic effects that can promote nerve regeneration and functional reinnervation. However, the combined impact of these hormones on peripheral nerve repair remains poorly understood. This study aimed to analyze the individual and combined effects of GH and GnRH in a rat model of SNT, using orchiectomized male rats to prevent steroid-mediated neuroregeneration and neuroprotection. Treatments included GH, GnRH, or a combination of both, with subsequent assessments of motor and sensory function, as well as histological and molecular analyses of the nerve tissue and associated muscles. The results revealed that both GH and GnRH significantly enhanced nerve regeneration and neural function when administered individually. Treated animals exhibited improved axonal growth, myelination, as well as sensory and motor functional recovery. In addition, GH and GnRH reduced neuroinflammation/reactive gliosis, as evidenced by the downregulation of TNFα IL-1β, Iba-1 and GFAP, which are typically elevated following nerve injury. These findings indicate that each hormone independently supports critical aspects of nerve repair and functional restoration after injury. Surprisingly, when GH and GnRH were administered together, their beneficial effects were not additive. Instead, the combination of the two treatments led to diminished outcomes in comparison to either treatment alone. Specifically, animals receiving the combined therapy showed reduced axonal organization, impaired myelination, and less functional improvement. In conclusion, GH and GnRH demonstrate potential as individual therapeutic agents for promoting nerve regeneration, each providing significant benefits in terms of axonal growth, functional recovery, and reduction of neuroinflammation.