Neurotrophic and Neuroregenerative Effects of GH/IGF1

Int J Mol Sci. 2017 Nov 17;18(11):2441. doi: 10.3390/ijms18112441.

Abstract

Introduction: Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects.

Methods: In the literature, we searched the clinical trials and followed up studies in humans, which have evaluated the effect of GH/IGF-1 on CNS and PNS. The following keywords have been used: "GH/IGF-1" associated with "neuroregeneration", "amyotrophic lateral sclerosis", "Alzheimer disease", "Parkinson's disease", "brain", and "neuron".

Results: Of the retrieved articles, we found nine articles about the effect of GH in healthy patients who suffered from traumatic brain injury (TBI), and six studies (four using IGF-1 and two GH therapy) in patients with amyotrophic lateral sclerosis (ALS). The administration of GH in patients after TBI showed a significantly positive recovery of brain and mental function. Treatment with GH and IGF-1 therapy in ALS produced contradictory results.

Conclusions: Although strong findings have shown the positive effects of GH/IGF-1 administration on neuroregeneration in animal models, a very limited number of clinical studies have been conducted in humans. GH/IGF-1 therapy had different effects in patients with TBI, evidencing a high recovery of neurons and clinical outcome, while in ALS patients, the results are contradictory. More complex clinical protocols are necessary to evaluate the effect of GH/IGF-1 efficacy in neurodegenerative diseases. It seems evident that GH and IGF-1 therapy favors the optimal recovery of neurons when a consistent residual activity is still present. Furthermore, the effect of GH/IGF-1 could be mediated by, or be overlapped with that of other hormones, such as estradiol and testosterone.

Keywords: 17β-estradiol; Alzheimer’s disease; IGF-1; amyotrophic lateral sclerosis; growth hormone; neuroregeneration; peripheral nerve regeneration; testosterone.

Publication types

  • Review

MeSH terms

  • Adult
  • Amyotrophic Lateral Sclerosis / therapy*
  • Animals
  • Brain Injuries / therapy*
  • Drug Evaluation
  • Growth Hormone / therapeutic use*
  • Humans
  • Insulin-Like Growth Factor I / therapeutic use*
  • Male
  • Mice
  • Middle Aged
  • Models, Animal
  • Neurons / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Treatment Outcome

Substances

  • Neuroprotective Agents
  • Insulin-Like Growth Factor I
  • Growth Hormone