Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver.
Individuals with Laron syndrome carry mutations in the GHR gene resulting in severe congenital IGF-1 deficiency and elevated GH serum levels leading to short stature as well as perturbed lipid and glucose metabolism.
Mutations in the human growth hormone receptor gene (GHR) are the most common cause of growth hormone insensitivity (GHI) syndrome and insulin-like growth factor (IGF-1) deficiency.
GH insensitivity (primary IGF-I deficiency) can be caused by genetic defects in GHR, STAT5B, IGF1, IGFALS, which all have their specific clinical and biochemical characteristics.
In man, evaluation of the 2 largest cohorts of patients with Laron syndrome (inactive GH receptor resulting in IGF1 deficiency) in Israel and Ecuador revealed that despite their dwarfism and marked obesity, patients are alive at the ages of 75-78 years, with some having reached even more advanced ages.
Growth hormone (GH) insensitivity and insulin-like growth factor-I deficiency in Inuit subjects and an Ecuadorian cohort: functional studies of two codon 180 GH receptor gene mutations.
Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years.
IGF-I deficiency is associated with prenatal and post-natal growth failure and may arise primarily as a result of GH receptor/post-receptor abnormalities or defects in the synthesis and transport of IGF-I.