Steroid receptors and the mechanism of the specificity of glucocorticoid responsiveness of somatic cell hybrids between hepatoma tissue culture cells and mouse fibroblasts

Hybrid cells prepared from hepatoma tissue culture (HTC) and mouse L cells were studied to gain more information concerning glucocorticoid induced functions. The hybrid cells contain phenotypic and chromosomal markers of both parents but fail to show HTC type responses. The authors show them to respond to glucocorticoids in a manner characteristic of the L cell parent. HTC, L and hybrid cells all contain high affinity saturable cytoplasmic glucocorticoid receptors. Studies of these cytoplasmic receptors in the hybrid suggest that receptors from both parents are present and capable of binding steroid inducers. In vitro studies reveal saturable high affinity binding of hybrid receptors from cytosol to homologous nuclei. Mixing experiments with various parental and hybrid cytosols and nuclei suggest that hybrid cells contain both parental cytoplasmic receptors and two classes of nuclear binding sites which can distinguish between the glucocorticoid receptors of the two parental cells. Results obtained in new hybrids derived from HTC cells and steroid resistant L cells suggest that failure to express HTC type responses to glucocorticoids is not a result of dominance of steroid provoked inhibitory effects derived from the L cell parent. In this cross between a receptor (-) L cell parent and a receptor (+) HTC cell parent the hybrid, which was receptor (+), did not show glucocorticoid response.