Freshly isolated human B-lymphocytes from eight subjects and Epstein-Barr virus-transformed human Blymphocytes from seven subjects were examined for their capacity to secrete insulin-like growth factor-I (IGF-I) and IGF-II and for their capacity to respond to human GH. Similar studies were conducted with Epstein-Barr virus-transformed lymphocytes collected from six African pygmies. When transformed B-lymphocytes from normal stature subjects were cultured for 3 weeks in RPMI-1640 medium (6 × 103 cells/75-cm2 flask at seeding), significant amounts of IGF-I, but no IGF-II, were produced. GH (150 ng/mL) significantly increased for control cells the amount of IGF-I produced at each sampling interval compared to that by unstimulated cultures (P < 0.05 at 1 week; P = 0.005 at 3 weeks). At 3 weeks, cell counts of cultures compared were 4.13 ± 0.39 × 106/mL for unstimulated cells and 4.23 ± 0.87 × 106/ mL for GH-stimulated cells. IGF-I production at this time interval by unstimulated cells was 2.8 ± 2.3 ng/mL, and that by GH-stimulated cells was 12.3 ± 2.5 ng/mL (P = 0.005). Cell multiplication rates of control cultures were increased in 1 week by GH stimulation [GH stimulated, [16.7 ± 22.0 × 104 cells, unstimulated, 5.73 ± 4.1 × 104 cells; (mean ± SD); n = 14; P < 0.01]. Similar results occurred with GH studied at a lower concentration of 10 ng/mL for 3 weeks. Freshly isolated Blymphocytes did not secrete IGF-I and -II after 5 days of culture with GH. Cultures established from cells derived from pygmies produced significantly less IGF-I (4.24 ± 2.62 ng/mL) when stimulated with 150 ng/mL GH than cultures of cells from normal stature subjects (12.3 ± 2.5 ng/mL; 0.005 < P < 0.01). The cultures compared had a similar cell density. A similar significant difference in IGF-I secretion occurred between cultures of pygmy and control cells stimulated with 10 ng/mL GH. These data are consistent with previous in vivo studies in which pygmies failed to increase IGF-I and exhibit metabolic responses to exogenous GH.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical