Murine glucocorticoid receptors and the H-2 locus--a reappraisal.
It has been demonstrated that susceptibility to glucocorticoid-induced formation of cleft palate is regulated by the mouse histocompatibility complex (H-2). This has encouraged us to examine H-2 effects on glucocorticoid binding in tissues of adult animals which would provide sufficient material with which to study the biochemical mechanism of the H-2 effect. Although it has been reported that cytosol prepared from lungs of adult mice with a high susceptibility to steroid-induced cleft palate formation have a higher level of glucocorticoid binding than lung cytosol prepared from a low-susceptibility strain, we are unable to demonstrate any influence of H-2 on binding capacity in this tissue from adult animals when glucocorticoid receptors are assayed in the presence of receptor reducing and stabilizing agents that maximize binding capacity. Cytosol prepared from rat liver contains an endogenous receptor-reducing system composed of NADPH and thioredoxin. It has also been reported that the murine H-2 complex contains a gene(s) that regulates the level of a modifier(s) in fetal hepatic cytosol that affects the binding of glucocorticoids to the receptor. Of two known low molecular weight modifiers that could account for this effect, we have previously established that the heat-stable, steroid receptor "modulator" is not regulated by the H-2 complex. In the present work we have assayed thioredoxin, a second potential modifier, in liver cytosols prepared from adults of two pairs of two H-2 congenic mouse strains. Our results show that the amount of thioredoxin is the same in all four mouse strains and that it is not regulated by the H-2 locus. At this time, we are unable to identify a system in adult mice in which the widely reported regulation of glucocorticoid binding by the mouse histocompatibility locus can be submitted to definitive biochemical study.
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D006183:H-2 Antigens / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009249:NADP / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism
D006183:H-2 Antigens; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D013879:Thioredoxins; D009249:NADP