Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor I.

Abstract

In the present study, the erythropoietic activity of fetal serum was characterized. Using fetal bovine serum (FBS) as a source of the erythropoietic activity and serum-free cultures of fetal mouse livers (FMLC assay) as a detection system, we found that FBS stimulated colony formation from late erythroid progenitor cells (CFU-E) in a dose-dependent fashion. The slope of the dose-response curve, however, was significantly different from that for erythropoietin (Ep), the best-characterized erythropoietic activity so far. The erythropoietic activity of FBS was found in the 120-160-and 40-70-kD range at neutral pH. In the presence of 1 M acetic acid, however, the erythropoietic activity had an apparent molecular mass between 3 and 13 kD. From ion exchange experiments with DEAE-cellulose, the isoionic point of the activity was estimated to about pH 5. Furthermore, the erythropoietic activity of FBS was found to be co-eluted on Sephadex G-150 with the binding proteins of insulinlike growth factors (IGF). The IGF I concentration determined by radioimmunoassay was 70 ng IGF I/ml. The Ep activity of FBS was <5 mU/ml when determined with the posthypoxic polycythemic mouse assay for Ep. These results suggest that the erythropoietic activity of FBS is related to IGF and not to Ep. The erythropoietic activity of FBS was abolished by an antiserum against IGF I. Furthermore, IGF I was a factor of -40 more potent than IGF II in stimulating erythroid colony formation. All of these findings suggest that the erythropoietic activity of FBS is IGF I.

Insulin-like Growth Factor I and Insulin-like Growth Factor Binding Protein 3 as Determinants of Blood Hemoglobin Concentration in Healthy Subjects

“…Earlier in vitro studies (3,4,(6)(7)(8)(9) lend support to speculations that the associations we observed indicate a causal relationship. In human cell cultures (6, 7) and in animal experiments (3-5, 8, 9), IGF-I stimulates erythropoietic colony and burst formations.…”

“…The serum concentration of the major IGF-binding protein (IGFBP-3) reflects the total amount of IGF-I and IGF-I1 in the circulation and the secretion of growth hormone similarly or even better than the serum concentration of IGF-I alone (2). IGF-I has a role in the regulation of the erythropoietic system in vitro and also in vivo (3)(4)(5)(6)(7)(8)(9). IGF-I stimulates proliferation of murine and human erythroid progenitor cells in bone marrow culture systems (4,6).…”

“…IGF-I has a role in the regulation of the erythropoietic system in vitro and also in vivo (3)(4)(5)(6)(7)(8)(9). IGF-I stimulates proliferation of murine and human erythroid progenitor cells in bone marrow culture systems (4,6). The optimum in vitro erythropoiesis appears to depend on several systems, including erythropoietin, stem cell factor, IGF-I, and unidentified factors (8,9).…”

Inactivation of the IGF-I receptor gene in primary Sertoli cells highlights the autocrine effects of IGF-I

“…A 1% serum provides no more than 0 . 7 ng IGF-I per ml of medium (Kurtz et al 1985), which is five-to ten-fold lower than the ED50 of IGF-I on Sertoli cells as reported in several studies (Jaillard et al 1987, Rappaport & Smith 1995. Under our experimental conditions, we found that more than 85% of Sertoli cells were infected by lentivirus.…”

Lysophosphatidic Acid Induces Necrosis and Apoptosis in Hippocampal Neurons

“…For example, transforming growth factor-/3 and insulin-like growth factor I protect against several neurotoxic insults (Cheng and Mattson, 1992;Zhang et al, 1993;Prehn eta!., 1994;Singleton eta!., 1996). These factors may also be protective with respect to LPA because neurons are often cultured in medium supplemented with serum that contains LPA and other mediators, including transforming growth factor-/3 and insulin-like growth factor I (Kurtz et a!., 1985;Honegger and Humbel, 1986;Masui et a!., 1986;Eichholtz et al, 1993;Tokumura et a!., 1994;Moulin et al, 1997).…”