副腎皮質に対する糖質コルチコイドの直接抑制作用に関する研究
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概要
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There is much evidence to suggest that cell proliferation and steroidogenesis of the adrenal cortex are regulated by adrenocorticotropin (ACTH). Recently, direct inhibitory effects of glucocorticoid on cell proliferation and steroidogenesis of the adrenocortical cells has also been suggested. However, contradictory data have been reported, and the possible physiological significance of such direct action of glucocorticoid remains to be established.<BR>A monolayer culture of mouse adrenal tumor cell line Y-1 was used to investigate the effects of glucocorticoid on cell replication, DNA synthesis, steroidogenesis and ACTH receptors of adrenocortical cells in an in vitro condition.<BR>In an in vivo human study, a rapid ACTH test was repeated twice on each of 5 healthy female volunteers at an interval of 2 weeks, with 2 and 12 mg of dexamethasone administered from 11-12 PM the previous night.<BR>The results obtained were as follows : <BR>1) Corticosterone at a concentration of 5.0, 50 μg/ml significantly inhibited cell replication and <SUP>3</SUP> H-thymidine incorporation into DNA of Y-1 cells in a dose-response manner.<BR>2) Corticosterone at a concentration of 0.5 to 50μg/ml significantly inhibited ACTH-induced steroidogenesis of Y-1 cells in a dose-response manner.<BR>3) However, the characteristics of the ACTH receptors of these cells remained unaffected by 0.5 to 50 μg/ml of corticosterone.<BR>4) When pretreated with 12 mg of dexamethasone, plasma cortisol response to ACTH in normal human volunteers at 30 min after the ACTH injection was significantly lower than that obtained after pretreatment with 2 mg of dexamethasone.<BR>The results of the in vitro study strongly suggest that glucocorticoid may play an important role in the regulation of cell proliferation and the function of the adrenocortical cells, and that the suppressive effect of corticosterone on ACTH-induced steroidogenesis is not attributable to a change in ACTH receptors or an ACTH-ACTH receptor interaction. The result of the in vivo human study, together with the in vitro study, suggest that the suppressive effect of glucocorticoid on steroidogenesis of the adrenal cortex at the adrenal level may exist in man.
- 日本内分泌学会の論文