Dissociation of systemic GH-IGF-I axis from a genetic basis for short stature in African Pygmies

Objectives: To test the hypothesis that the primary cause of short stature in African Pygmies resides in low levels of insulin-like growth factor I (IGF-I), and to evaluate whether any observed alterations in their systemic IGF-I status can be dissociated from the effects of malnutrition and/or altered immune status. Setting: Expedition to camps of partially sedentarized African Pygmies and neighbouring Bantu farmers living in the equatorial rain forest of Eastern Cameroon. Design: Serum assays for hormonal and immune status were conducted for individuals (children, adolescents, young and old adults) showing no overt clinical nor biochemical signs of malnutrition, as judged from anthropometry, clinical examinations and serum assays of albumin, pre-albumin, retinol-binding protein, transferrin, iron, zinc, magnesium and calcium. Results: African Pygmies did not differ from Europeans or Bantus in mean serum IGF-I concentrations, nor in the relationship between serum IGF-I and its major binding protein (IGFBP-3). However, although in both African groups the immunoglobulins IgG, IgM and IgE as well as the C-reactive protein and ceruloplasmin were above the normal range of European references, the Pygmies differed from their Bantu neighbours in their much higher IgG and IgM serum levels. A plot of serum IGF-I against these immunoglobulins in Pygmies revealed a reverse sigmoidal relationship, with the low IGF-I values associated with serum levels of IgG and IgM which clearly exceeded those found in the Bantus. Conclusions: This study indicates that in growing and adult African Pygmies showing no clinical nor biochemical signs of nutritional deficiency, serum IGF-I and IGFBP-3 (hence IGF-I bioavailability to its receptors) are essentially normal, and that low circulating levels of IGF-I in Pygmies reside in differential exposure and/or responsiveness to environmental challenge (e.g. infections) rather than in an inherited defect in the systemic growth-hormone (GH)-IGF-I axis. Sponsorship: Supported by the Roche Research Foundation. Descriptors: growth, stature, malnutrition, infection, IGF-I, growth hormone (GH)-IGF-I axis.