Sustained High Insulin-Like Growth Factor-Binding Protein 3 Levels after Suppression of Gonadal Steroids in Central Idiopathic Precocious Puberty

Abstract

The direct role of sex steroids in pubertal bone growth may be an increased growth hormone (GH) receptor-coupled GH action. We previously reported that suppression of sex steroids by a gonadotropin-releasing hormone (GnRH) agonist (leuprolide acetate) increases the activity of serum growth hormone-binding protein (GHBP), identical to the extracellular domain of GH receptor, in central idiopathic precocious puberty (CIPP). Since insulin-like growth factor (IGF) -binding protein 3 (IGFBP-3) is a GH-dependent IGF binding protein, we measured IGFBP-3 and GHBP before and after treatment with the GnRH agonist in eight children with CIPP. IGFBP-3 and GHBP were measured by radioimmunoassay and immunoprecipitation.The treatment suppressed gonadal function. The initial IGFBP-3 level was high. After the treatment, IGFBP-3 remained at this level despite a reduction in GH secretion. There was a significant positive correlation between IGFBP-3 level and GHBP activity (r=0.63, p<0.01).The high IGFBP-3 level in a patient with CIPP is presumed to result from increased GH secretion, similar to the GH-dependent increase in IGF-I. Although we can not explain the sustained increase in IGFBP-3 after gonadal suppression, the high IGFBP-3 level may interfere with the growth promoting effect of IGF-I.