Abstract
AT physiological temperatures glucocorticoids1–5, in common with other steroid hormones6, initially interact with normal target cells such as the rat thymocyte by forming hormone–receptor complexes that seem first to be located in the cytoplasm and then rapidly become bound to the nucleus. At low temperatures (0–4 °C) the hormones, when incubated either with target cells or with cytosols from such cells, form ‘non-activated’ complexes that do not bind to nuclei; subsequent warming of the cells1–5, or of the cytosols together with nuclei2,7–11, leads to the formation of nuclear-bound complexes. As shown originally with oestrogens12 and later with glucocorticoids2,7–10,13, if cytosols with non-activated complexes formed at 0–4 °C are warmed to 20–37 °C in the absence of nuclei, the complexes become ‘activated’, and will then bind to nuclei even at low temperatures. Activation, which can also be brought about by increased ionic strength7–9,13, gel filtration, dilution and other treatments14, has been studied extensively and is known to be accompanied by several changes other than enhanced affinity for nuclei. For glucocorticoid–receptor complexes the changes include enhanced affinity for DNA7,10,13–15 and altered mobility on phosphocellulose16, DEAE-Sephadex17 and DEAE-cellulose18 columns. This last property is the one we have used in our experiments. Despite the many published studies on activation, formation of non-activated complexes and subsequent activation have apparently never been demonstrated in cells or cytosols exposed to steroids at normal body temperatures only. Consequently, it is not known whether non-activated complexes and activation have any significant role in physiological conditions, and at least one well known scheme of steroid hormone action19 does not include the activation step. It is therefore possible that when steroid hormones bind to cytoplasmic receptors at physiological temperatures they immediately form activated complexes. The results described here show that for glucocorticoids this alternative can be excluded: when these steroids interact with receptors in rat thymus cells at 37 °C they initially form non-activated complexes, and subsequently give rise to activated complexes.
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MUNCK, A., FOLEY, R. Activation of steroid hormone–receptor complexes in intact target cells in physiological conditions. Nature 278, 752–754 (1979). https://doi.org/10.1038/278752a0
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DOI: https://doi.org/10.1038/278752a0
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