Decreased insulin-like growth factor I receptor expression and function in immortalized African Pygmy T cells

The Journal of Clinical Endocrinology and Metabolism
Y HattoriD W Golde

Abstract

Efe Pygmies of northeast Zaire have the shortest mean adult stature of any population on earth. Although various alterations in the GH/insulin-like growth factor I (IGF-I) axis have been suggested, the basis for short stature in the Pygmy is unknown. We previously described IGF-I unresponsiveness in a T lymphoblast cell line derived from an Efe Pygmy, and studies in five additional lines have confirmed severe IGF-I resistance in these cells. We have now performed experiments to determine the molecular basis for the IGF-I resistance in these cells. We found markedly decreased cell surface expression of IGF-I receptors with normal ligand binding affinity. The Pygmy IGF-I receptors were not autophosphorylated and did not transmit a signal in response to physiological concentrations of IGF-I. There was a substantially decreased level of IGF-I receptor messenger ribonucleic acid in the Pygmy cells with a normal messenger ribonucleic acid half-life. The nucleotide sequence of the full-length IGF receptor complementary DNA in Pygmy 1 showed no significant variation. These results indicate decreased IGF-I receptor gene transcription and IGF-I receptor signaling as the primary variation in the Pygmy cell lines. The findings point to the...Continue Reading

Citations

Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·A MorrioneR Baserga
Mar 25, 2009·Genome Research·Joseph K PickrellJonathan K Pritchard
Jul 21, 2001·Molecular and Cellular Biology·K S Rajavel, E F Neufeld
Nov 5, 2010·PloS One·Fernando V Ramírez Rozzi, Marina L Sardi
Oct 12, 2000·Domestic Animal Endocrinology·P Sellier
Nov 23, 2010·American Journal of Physical Anthropology·Robin M Bernstein
Jan 26, 2006·Endocrine Reviews·Johannes D VeldhuisCyril Y Bowers

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