Evaluación de los niveles séricos de la proteína de unión de alta afinidad de la hormona de crecimiento humana (GHBP) y del polimorfismo del exón 3

MARÍA G BALLERINI1*, PAULA SCAGLIA2, HORACIO M DOMENÉ2, ALICIA MARTINEZ2, ANA KESELMAN2, VIVIANA PIPMAN3, SONIO V BENGOLEA4, HAMILTON CASSINELLI1, LILIANA KARABATAS2, MARÍA L CALCAGNO5, JUAN J HEINRICH1,

REVISTA ARGENTINA DE ENDOCRINOLOGIA Y METABOLISMO

SOCIEDAD ARGENTINA DE ENDOCRINOLOGÍA Y METABOLISMO

Año: 2009

0080-2077

Summary Idiopathic Short Stature (ISS) includes a heterogeneous group of children with growth failure. One possible explanation for the growth failure is a reduced responsiveness to growth hormone (GH). Human circulating GH is partially bound to a high-affinity binding protein (GHBP) which is derived from proteolytical cleavage of the extracellular domain of the GH receptor. Many reports have demonstrated a close relationship between GHBP and liver GH receptor status in physiological conditions and diseases. Moreover, serum GHBP measurement has been proposed as an useful peripheral index of GH receptor abundance. Our objective was the evaluation of serum GHBP levels and its probable association with serum growth factors (IGF-I, IGFBP-3 and ALS) and the exon 3 polymorphism of the extracellular domain of the GHR gene in ISS children. Children with ISS presented significantly lower height SDS, BMI SDS, serum components of the IGFs system and GHBP concentration as compared to an age-matched control group of normal children (p<0.001). Interestingly, exon 3 genotype did not influence the differences observed in these parameters. The maximal GH response obtained after two GH provocative tests inversely and significantly correlated to GHBP serum levels (r= -0.28, p= 0.012). A frequency study showed a deviation to low SDS values of serum GHBP, IGF-I, IGFBP-3 and ALS. Conclusion: 1- in children with ISS the exon 3 genotype of the GHR gene is not a factor that could explain the lower levels observed in circulating GHBP concentration and components of the IGFs system; 2- low serum GHBP together with low IGF-I, IGFBP-3 or ALS levels would help pointing to GH insensitivity due to GH receptor gene abnormalities in ISS.