ESPE Abstracts (2015) 84 P-2-400

Regulation of IGF1R mRNA Expression by GnRH Agonist may be Involved in the Decrease of Height Velocity During Central Precocious Puberty Therapy

Mariana Sarti De Paula, Rafaela Ricco, Rodrigo Custodio, Soraya Milani, Patricia Atique, Ayrton Moreira, Sonir Antonini, Raphael Liberatorejr & Carlos Martinelli jr


Fmrp-Usp, Ribeirao Preto, Brazil


Background: Growth spurt is a major event in central precocious puberty (CPP). GnRH analogue (GnRHa) therapy inhibits gonadal axis and decreases height velocity. However, serum IGF1 and IGFBP-3 remain high as before therapy. Reports on IGF type 1 receptor (IGF1R) in CPP are yet unavailable.

Aim: To study IGF1R mRNA expression in girls with CPP before and during GnRHa therapy.

Methods: 34 girls with CPP were studied. Sixteen of them (8.0±0.7 years) were evaluated before (group A) and 18 (9.4±0.8 years) during GnRHa therapy (group B). Age-matched prepubertal girls were studied as controls (n=18). Fasting blood samples were collected for IGF1R mRNA expression in peripheral lymphocytes (RT-PCR) and serum IGF1, IGFBP-3, IGFBP-1 and insulin analysis.

Results: IGF1R mRNA expression was higher in group B than in group A (P=0.04) and control (P=0.03). No significant difference was observed between group A and control. IGF1, IGFBP-3 and IGF1/IGFBP3 molar ratios were similar in groups A and B but lower in control (P<0.0001). IGFBP-1 was higher (P<0.0001) in control than in groups A and B. IGBPB-1 was also higher in group A than in group B. Insulin levels were lower in control than in group A (P=0.01), but no significant difference was observed between groups B and A. Six girls were studied at two moments, before and during GnRHa therapy. In this group, IGF1R mRNA expression was also higher during GnRHa therapy (P<0.01) while IGF1, IGFBP3 and IGF1/IGFBP3 molar ratios were similar in both evaluations.

Conclusion: The decrease in height velocity during CPP therapy with GnRHa cannot be explained by changes in IGF1 availability. However, the increase in IGF1R mRNA expression suggests impairment of IGF1 signalling with compensatory up regulation of IGF1R. Increased GH concentrations due to reduction of IGF1 feedback could explain the IGF1, IGFBP-3 and IGFBP-1 findings.