Comparison of the growth hormone, IGF‐1 and insulin in cerebrospinal fluid and serum between patients with motor neuron disease and healthy controls

Abstract

Neurotrophic effects of the growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin on the central nervous system have become more apparent in the past decade. In this study, we measured serum and cerebrospinal fluid (CSF) concentrations of GH, IGF-1 and insulin in 35 patients with motor neuron disease (MND) [24 patients with definite amyotrophic lateral sclerosis (ALS) and 11 patients with progressive bulbar palsy] and in 40 healthy controls. Levels of serum concentrations of GH and IGF-1 did not significantly differ between the MND patient group and the healthy controls, while the level of insulin was significantly decreased (P = 0.0033) in the MND patient group. However, levels of all three examined parameters in CSF were significantly lower in the MND group than in the healthy controls with the statistical significance for IGF-1 and insulin of P < 0.001. This finding has not been reported previously, and further investigations into its association with ALS should establish whether it can be used as an early marker of the disease, or whether it merely represents a consequence of ALS development.

Calcium-dependent protein folding in amyotrophic lateral sclerosis

“…IGF-I levels were higher and IGF-II levels were significantly lower in patients with ALS than in healthy controls [142,143], suggesting that motor neuron degeneration could lead to a compensatory increase in IGF-I to provide additional support for motor neurons. On the other hand, decreased IGF-I levels were also found in cerebrospinal fluid of ALS patients [144], however, methodological differences and the lack of age-, gender-and BMI-matched control populations in these studies may account for these discrepancies. IGF-I and IGF-II can cross the blood brain barrier [145] and intrathecal administration of IGF-I to transgenic SOD1 G93A mice improved motor performance, delayed the onset of clinical disease, and extended survival [146], probably due to its augmentation of UPR.…”

Extrapituitary growth hormone

“…This homology extended over a region spanning nucleotides 65 to 659 of pituitary GH cDNA that coded for amino acids 4-201 (reviewed in 1). GH has also been detected in human cerebrospinal fluid (CSF) [21], and may reflect sequestration through the blood-brain barrier [22], although as the concentration is lowered in patients with neural degeneration [23,24], it is likely to reflect neural GH production. Within the nervous system, roles for GH in neural development are now well established and have been reviewed in recent years [25][26][27][28].…”

Dose-specific or dose-dependent effect of growth hormone treatment on the proliferation and differentiation of cultured neuronal cells

“…Lack of the growth factor is recent hypotheses about the mechanisms underlying motor neuron death in ALS [20]. In addition, GH, IGF-1 and insulin concentrations in CSF were significantly lower in ALS patients in comparison with the control group [21].…”