Endocrinology, Vol 124, 2289-2296, Copyright © 1989 by Endocrine Society

ARTICLES

The binding characteristics and biological effects in FRTL5 cells of placental protein-12, an insulin-like growth factor-binding protein purified from human amniotic fluid

AG Frauman, S Tsuzaki and AC Moses
Charles A. Dana Research Institute, Boston, Massachusetts.

We have studied the binding of recombinant human insulin-like growth factor I (hIGF-I), and hIGF-II, and rat IGF-II [rIGF-II (multiplication- stimulating activity)] to the human amniotic fluid IGF-binding protein placental protein-12 (PP12). PP12 displayed a 5- to 10-fold higher affinity for IGF-I compared to hIGF-II or rIGF-II. These differences in binding affinity were confirmed by both saturation binding analysis and competitive binding analysis using 125I-labeled IGF-I, hIGF-II, and rIGF-II and each of the unlabeled ligands. PP12 produced dose-dependent inhibition of IGF-I-stimulated [3H]thymidine incorporation in the rat thyroid follicular cell line FRTL5. Inhibition of IGF-I-stimulated thymidine incorporation paralleled the ability of PP12 to inhibit IGF-I binding to the surface of FRTL5. At a high concentration, PP12 also inhibited TSH-stimulated DNA synthesis but did not inhibit the binding of 125I-labeled TSH to FRTL5. Insulin did not inhibit the binding of 125I-labeled IGFs to PP12, and PP12 did not inhibit the ability of insulin to stimulate DNA synthesis. These data suggest that the ability of PP12 to inhibit TSH-stimulated DNA synthesis is through the inactivation of IGF produced endogenously by FRTL5. Low concentrations of PP12 produced a statistically significant enhancement of TSH- stimulated DNA synthesis; the mechanism by which this occurs remains unclear.

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