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Functionality of the liver glucocorticoid receptor during the life cycle and development of a low-affinity membrane binding site

Parchman, L.G., Cake, M.H.ORCID: 0000-0002-5899-7291 and Litwack, G. (1978) Functionality of the liver glucocorticoid receptor during the life cycle and development of a low-affinity membrane binding site. Mechanisms of Ageing and Development, 7 . pp. 227-240.

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The ability of the liver glucocorticoid receptor to bind steroid and translocate to the nucleus in vivo was examined in order to elucidate possible developmental factors in the receptor system which block its action in fetal rat liver. Using optimal doses and uptake times of [3H]-dexamethasone established for the liver of adrenalectomized adult males, we found fetal livers to be capable of specific glucocorticoid binding by cytoplasmic receptors and of in vivo translocation of the bound steroid to nuclei. Although the specific binding in the cytosol was lower than 2nM in the late fetus, this could be accounted for by occupation of receptor binding sites by endogenous corticosterone present in extremely high concentrations in fetal plasma. The nuclear binding of dexamethasone, on the other hand, was as great in the late fetal liver as in adult liver, indicating that fetal liver cells were very efficient at nuclear translocation of receptor complex. These studies of in vivo nuclear binding of dexamethasone demonstrated that inhibition of glucocorticoid action before birth is due to some event other than the entry of glucocorticoid receptor into the nucleus. The receptor is present and functional in nuclear translocation at all developmental stages examined.

When nuclei from adults were assayed for dexamethasone binding in vitro, a lower- affinity, but saturable, binding component was present in large amounts. This membrane binding site of glucocorticoids was absent in nuclei from fetuses and newborn rats, and was not correlated with the appearance of glucocorticoid receptor in liver nuclei. Adult microsomal membranes contained even more low affinity glucocorticoid binder than nuclei. The presence of a high-affinity nuclear receptor was not detectable by the in vitro exchange assay of adult nuclei.

Item Type: Journal Article
Publisher: Elsevier
Copyright: © 1978 Published by Elsevier Ireland Ltd.
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