This article presents a comprehensive overview of the physiological, cellular, biochemical, and molecular actions of glucocorticoids. Emphasis is placed on the structure of the glucocorticoid receptor, the process known as receptor activation, and the function of endogenous regulators in receptor-mediated signal transduction. The role of receptor phosphorylation, and the activities of exogenous sodium molybdate, are also reviewed. In addition, recent advances in the structure and mechanism of action for the low mol wt heat-stable "modulator" of glucocorticoid receptor activity are also discussed. Modulator is a novel ether aminophosphoglyceride that appears to be the "endogenous molybdate factor." A model is presented for the interaction of modulator with the glucocorticoid receptor. This model seeks to explain the actions of sodium molybdate toward the glucocorticoid receptor, and perhaps toward other steroid-hormone receptors as well. Finally, results from an ultra-large scale purification of two new modulator isoforms, and the activities of these isoforms toward the glucocorticoid receptor, the mineralocorticoid receptor, and protein kinase C, are also summarized.

Animals↗

PubMedDate not supplied

Efficacy of pyridoxal treatment in controlling the growth of melanomas in cell culture and an animal pilot study.

We have demonstrated, using confocal laser scanning microscopy, that pyridoxal treatment of B16C3 murine melanoma cells inhibits triamcinolone acetonide induced translocation of the glucocorticoid receptor to the nucleus of intact cells. In addition to inhibiting glucocorticoid receptor nuclear translocation, pyridoxal kills B16C3 murine melanoma cells and WM983A human melanoma cells in culture. Cortexolone, a glucocorticoid antagonist, also kills cells in culture. This mechanism, however, appears to initiate in the glucocorticoid receptor signal transducing cascade at a point prior to the impact of pyridoxal treatment alone. The glucocorticoid antagonist RU486 has no detrimental effect on melanoma cell viability, however, in combination with pyridoxal, RU486 extends cell viability. Since pyridoxal kills melanoma cells in culture, a pilot study was carried out examining the efficacy of topical application of a pyridoxal cream to inhibit the growth and/or cause regression of (B16C3) xenograft melanoma tumors in an immunocompetent (Hairless Rhino-J3) and an immunocompromised (Crl: nu/nu (CD1)BR) murine animal model. The results of the study with immunocompetent animals are encouraging. While tumors are brought under control by pyridoxal treatment, further work is needed to determine the most efficacious treatment regimen and to establish formal concentrations for pyridoxal in topical ointments. Trials using immunocompromised animals indicated that although some qualitative differences may be detected between the control and experimental animals, tumor growth in these animals is so aggressive that multiple applications or higher concentrations of pyridoxal may be needed to obtain useful data.

Administration, Topical↗