Growth hormone prevents human immunodeficiency virus–induced neuronal p53 expression

Abstract

Growth hormone (GH) is neuroprotective, presumably through its actions on GH receptor–mediated pathways. Here, we examined the effects of GH using in vitro and in vivo assays of human immunodeficiency virus (HIV)–induced neuronal injury. Neuronal cultures were in assays of neurotoxicity induced by supernatants from HIV‐1 tat‐transfected monocytoid cells (Tat supernatant). GH treatment reduced neuronal death compared with untreated cultures (p < 0.001), which was blocked by a GH receptor antagonist, B2036. Tat supernatant–induced p53 expression in neurons was also reduced by GH treatment. Expression of both p53 and GH receptor were increased in brain tissue from HIV‐infected persons compared with controls (p < 0.05). Mice receiving intrastriatal implants of Tat supernatant and treated with GH showed less neurobehavioral abnormalities together with reduced neuroinflammation and neuronal injury compared with untreated animals (p < 0.01). Three acquired immunodeficiency syndrome–defined patients with neurocognitive impairment were serially evaluated during daily GH treatment showing a sustained improvement in neuropsychological performance (p < 0.01). GH prevents neuronal death through its actions on neurons involving a p53‐mediated pathway and also improved in vivo neurological function, indicating that GH may have a role in the treatment of HIV‐induced neurodegeneration. Ann Neurol 2003;54:605–614