AN ENDOGENOUS SIGNAL TRIGGERING ERYTHROID-DIFFERENTIATION - IDENTIFICATION AS THYROID-HORMONE

The identification of thyroid hormone as an endogenous signal for eryt hroid differentiation began with our studies on the spontaneously diff erentiating murine erythroleukemia clone 3-1. We observed that the spo ntaneous differentiation frequency was dependent on a heat stable fact or present in fetal calf serum or calf bone marrow. We also noted that the bone marrow extract stimulated erythroid colony-forming units in mouse bone marrow cells, suggesting the relevance of this factor in no rmal erythroid differentiation. The bone marrow extract did not suppla nt the requirement of erythropoietin but was synergistic. Purification of the bone marrow extract indicated that the differentiation-inducin g activity for clone 3-1 cells cochromatographed with a low-molecular- weight, UV (280 nm)-absorbing component(s). These observations and pre vious reports identifying the avian erythroblastosis virus oncogene v- erbA as a mutated thyroid hormone receptor which blocked erythroid dif ferentiation led us to test thyroid hormone in our assay. Both triiodo thyronine and thyroxine were highly active, and the active constituent s in the chromatographically purified fraction were identified as trii odothyronine and thyroxine. Although thyroid hormone action has been a ssociated with both in vivo and in vitro erythroid differentiation, it s role has been often relegated to a secondary status. We suggest that thyroid hormone is required for the commitment of erythroid cells to terminal differentiation.