title: The shortness of Pygmies is associated with severe under-expression of the growth hormone receptor.
abstract: The stature is a highly heritable trait controlled by genetic and environmental factors. The African Pygmies represent a paradigmatic example of non-disease-related idiopathic short stature (ISS), showing a similar endocrine profile of Caucasian individuals with ISS. Pygmy children show normal anthropometric and endocrine parameters until puberty, while adult Pygmies show normal baseline and post-stimulation serum growth hormone (GH) levels but low values of baseline serum GH-binding protein (GHBP) and insulin-like growth factor-I (IGF-I). This discrepancy suggests a defective response to GH occurring in adulthood since Pygmies lack both the pubertal serum IGF-I surge and the growth spurt. However, sequencing of the key genes of the GH-IGF-I axis failed to identify Pygmy specific variants or haplotypes. We therefore aimed at assessing whether the quantitative gene expression profile of two key genes of the GH-IGF-I axis, GH and GHR, was also similar in low-stature and normal stature populations. We showed that the GH gene expression is 1.8-fold reduced and the GH receptor (GHR) gene expression is 8-fold reduced in adult Pygmies in comparison with sympatric adult Bantu, and that this reduction is not associated with sequence variants of the GHR gene. The marked decrease of the GHR expression in Pygmies is associated with reduced serum levels of the IGF-I and GHBP. Our results, documenting a markedly reduced GHR gene expression in adult Pygmies, could contribute to elucidate the mechanisms involved in ISS in Caucasoid subjects.
authors.affiliation: Pediatric Department, University of Pavia, Pavia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bozzola
authors.forename: Paola
authors.initials: P
authors.lastname: Travaglino
authors.forename: Nicola
authors.initials: N
authors.lastname: Marziliano
authors.forename: Cristina
authors.initials: C
authors.lastname: Meazza
authors.forename: Sara
authors.initials: S
authors.lastname: Pagani
authors.forename: Maurizia
authors.initials: M
authors.lastname: Grasso
authors.forename: Maithè
authors.initials: M
authors.lastname: Tauber
authors.forename: Marta
authors.initials: M
authors.lastname: Diegoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Pilotto
authors.forename: Eliana
authors.initials: E
authors.lastname: Disabella
authors.forename: Paolo
authors.initials: P
authors.lastname: Tarantino
authors.forename: Agnese
authors.initials: A
authors.lastname: Brega
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
mesh_terms: D000328:Adult; D000349:Africa; D001827:Body Height; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein