Mechanism of the glucocorticoid regulation of growth of the androgen-sensitive prostate-derived R3327H-G8-A1 tumor cell line.
The R3327H-G8-A1 cell line derived from the Dunning rat prostate adenocarcinoma contains both androgen and glucocorticoid receptors. Following steroid deprivation, androgens specifically increase the concentration of their receptors in these cells by approximately 2-fold within 6 h and 3-4-fold in 24 h. In the presence of potent glucocorticoids, androgen receptor augmentation is reduced by 40-50% in the first 6 h and completely inhibited during the subsequent 24 h. This event, which is specific for glucocorticoids, appears to be due to an inhibition of androgen receptor synthesis. Furthermore, glucocorticoids inhibit proliferation of these cells by inhibiting the release of growth factors and arresting them in the G0 or A state of the cell cycle. This inhibition can be overcome by addition of low concentrations of either epidermal growth factor or platelet-derived growth factor; however, the inhibitory effect of the glucocorticoid on androgen receptor augmentation is not released. These results suggest that glucocorticoids arrest cellular proliferation by altering the autoregulation of growth and that this event is not dependent upon inhibition of androgen receptor augmentation.
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001769:Blood; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004963:Estrenes / Q000378:metabolism / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007399:Interphase; D007700:Kinetics; D008297:Male; D015741:Metribolone; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D000728:Androgens; D004963:Estrenes; D005938:Glucocorticoids; D010982:Platelet-Derived Growth Factor; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D013196:Dihydrotestosterone; D015741:Metribolone; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D014222:Triamcinolone Acetonide