Assessment of growth hormone insulin like growth factor-I axis in Down’s syndrome

Abstract

As GH therapy has been reported to increase growth velocity in children with Down's syndrome (DS), we studied the GH-IGF-I axis in some DS patients affected by growth retardation without serious congenital malformation, malnutrition or pathological thyroid or adrenal function. IGF-I and IGF-II were evaluated in 39 patients in basal conditions. The patients were subsequently divided into two groups with respect to the IGF-I basal value: Group 1 (GR 1) consisting of patients with abnormally low basal IGF-I concentration as compared to age matched control subjects, group 2 (GR 2) consisting of patients with IGF-I in the normal range. In 6 GR 1 patients and 12 GR 2 patients we evaluated GH and IGF-I concentrations after stimulation with arginine (0.5 g/kg bw), and recombinant GH (4 IU im). In the same patients, GH radioreceptor assay and serum GH-binding protein were evaluated. In all patients IGF-II proved normal (534 +/- 23 ng/ml; mean +/- SE), while IGF-I was pathological in 36% of subjects. The cause of the defective IGF-I secretion in these patients does not seem to depend on an impaired GH axis, as no significant difference in arginine-stimulated GH peak values was seen between GR 1 (29.6 +/- 5.3 ng/ml) and GR 2 (15.1 +/- 2.24 ng/ml). IGF-I concentration evaluated 12, 24, and 48 h after arginine stimulation was significantly increased only in GR 2 patients (peak value: 0.95 +/- 0.1, p = 0.0003 vs baseline; GR 1: 0.34 +/- 0.05 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

“…It acts through IR/IGF-IR, IRS, and RAS/MAPK or PI3K/AKT in regulating neurogenic cell fate [125]. Decreased levels of IGF-I have been found to associate with growth retardation in DS patients, which could be rescued by GH therapy [126,127]. In addition, the insulin receptor knockout mouse suggests that neurons without insulin receptor exhibit significant reduction of Akt and Gsk3beta and increased tau hyperphosphorylation, characteristics of neurotoxicity in DS and AD [128].…”

β-Adrenergic Hyperresponsiveness in Compensated Hypothyroidism Associated with Down Syndrome

“…On the basis of these data, it is conceivable that any end-organ resistance in DS is partial, rather than complete. We should emphasize that severe short stature, common to both subgroups of DS in our study (Table 1), is a cardinal characteristic of DS and is not associated with GH deficiency (27,28) or any other endocrinopathy.…”

Human Ageing and the Growth Hormone/Insulin-Like Growth Factor-I (GH/IGF-I) Axis - The Impact of Growth Factors on Dementia

“…Some authors reported reduction of IGF-I levels in DS patients, without any age-related differences, to an extent similar to that in GHD patients [165,[170][171][172], while others showed a progressive decrease during advacing age, although within the age-related normal range [173]. Nutritional, lifestyle and/or social differences may explain these controversial findings.…”

“…Nutritional, lifestyle and/or social differences may explain these controversial findings. Both hepatic and cerebral IGF-I receptors seem preserved in DS that, in fact, show normal IGF-I sensivity to exogenous GH administration as well as normal GH binding proteins [163,170,172].…”

“…Low GH response to L-DOPA and clonidine, two indirect GH-releasing agents, have been shown in prepubertal DS patients, while normal arginine-as well as GHRH-induced GH rise was reported in DS children [171][172][173][174][175][176]. Normal GH response in DS children was also observed after maximal provocative stimuli, such GHRH combined with pyridostigmine or arginine, as well as after hexarelin, a synthetic GH secretagogue mimicking ghrelin action [173,176,177].…”