I Pigmei, modello paradigmatico di bassa statura idiopatica

Abstract

Objective: African Pygmies are one of the shortest population in the world and understanding the biological bases of their small size could help us to better comprehend the cause of idiopathic short stature in Caucasian children. The aim of this study was to investigate if the short stature, the reduced growth velocity and the dysfunction of GH/IGF-I axis of Pygmies are due to genetic mechanisms. Design: 35 Baka Pygmy adults (22 females and 13 males; age 36±15 years) and 14 Bantu adults (3 females and 11 males; age 37±10 years). We evaluated serum levels of GH, GHBP and IGF-I and the quantitative expression of GH and GHR genes in both populations. Methods: blood samples were collected in Tempus Blood™ RNA tubes. Serum GH and IGF-I were measured with a fully automated immunochemistry analyzer, Immulite 2000. Serum GHBP were detected with ELISA assay. In order to evaluate gene-expression of GH and GHR genes, the total RNA was extracted and amplified through Real Time PCR and then turned in single-strand DNA. Polymorphisms of GHR gene were investigated through capillary electrophoresis. Results: serum GH levels were not different between the two populations, whereas IGF-I and GHBP levels were significantly lower in Pygmies than in Bantu. GH and GHR quantitative gene-expression resulted lower in Pygmies than in Bantu. Finally, no polymorphisms in GHR gene were found. Our data show that Pygmies have lower serum IGF-I and GHBP levels than Bantu and a reduction in quantitative expression of GH and GHR genes. These results could be a starting point for further studies aimed at finding epistatic and epigenetic effects. The evaluation of GH secretion with the Immulite assay using the 98/574 recombinant human GH as a calibrator revealed blunted GH secretion in 15 out of 18 subjects, confirming the clinical diagnosis of GHD. Subsequently, we measured GH levels in the same samples using IS 80/505 pituitary derived GH as a calibrator, and found reduced GH levels only in 11 children. Conclusions: these data confirm that GH values may depend on different calibrators used in the GH assay, and these calibrators affect the formulation of GHD diagnosis and the consequent decision to start GH substitutive treatment.