Effect of high level of endogenous corticosterone on glucocorticoid receptors in the spleen of rats bearing AH130 tumors.
Increase in spleen weight and in the number of spleen cells was observed in rats bearing AH130 (solid-type) tumors, which have high plasma corticosterone concentrations. In contrast, decrease in the number of spleen cells was observed in adrenalectomized rats without tumors which were injected every 3 hr with a dose of corticosterone sufficient to produce a plasma level close to the physiological range in rats with advanced stage tumors. In the spleen of adrenalectomized, corticosterone-treated rats, the binding capacity and affinity of cytosol receptors for dexamethasone decreased and were low on day 3 after the last injection of corticosterone, when no corticosterone was detectable in the spleen and the receptors in the liver cytosol showed maximal binding capacity. Neither the level of cytosol receptors in the spleen nor their affinity for dexamethasone, however, were changed in tumor-bearing rats on day 3 after adrenalectomy when the level of cytosol receptors and affinity for steroid of the thymus were still very low. The activity of alanine aminotransferase increased appreciably in the spleen cytosol of glucocorticoid-treated rats, but not in tumor-bearing rats, which have high plasma corticosterone levels. These data show that administration of corticosterone at physiological concentrations affected the spleen cells, the glucocorticoid receptors and alanine aminotransferase, but that in AH130 tumor-bearing rats, which have a high level of endogenous corticosterone, the spleen enlarged without change in the above parameters. Thus spleen cells from rats with tumors were more resistant to glucocorticoid than those from animals without tumors. However, there seemed to be no correlation between the level of glucocorticoid receptors and glucocorticoid resistance.
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000315:Adrenalectomy; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D014444:Tyrosine Transaminase; D003345:Corticosterone