Regulation of Dexras 1 expression by endogenous steroids

Dexras1, a newly identified member of the Ras superfamily of proteins, was discovered in AtT-20 corticotrope cells because its expression was induced in response to glucocorticoids (dexamethasone; Dex). As yet, the function o f Dexras1 is unknown, but its rapid induction in response to glucocorticoid s suggests the possibility that it may be involved in negative feedback reg ulation of corticotropin secretion. To better understand the control of Dex ras1 expression, possible effects of other steroid hormones on its expressi on were studied in both AtT-20 cells and in mouse pituitaries. AtT-20 cells were treated with each of 6 steroids [aldosterone, corticosterone (Cort), Dex, beta -estradiol (E-2), progesterone and testosterone] for 2 h. Dexras1 expression was assessed using both reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis. Expression of the gene was only in duced in response to glucocorticoid treatment (Dex or Cort). The 6 steroids were also injected into mice, pituitaries were harvested and total RNA was obtained for RT-PCR analysis. Surprisingly, treatment with E-2, not only i njection of glucocorticoids, induced Dexras1 expression in mouse pituitary. Other steroids were without effect. The results suggest that in AtT-20 cor ticotropes, Dexras1 expression is only induced by glucocorticoid-type stero ids. In pituitary glands of mice, the gene's expression is also responsive to E-2. We conclude that either Dexras1 expression in corticotropes from no rmal mice is regulated differently from that in AtT-20 cells, or that Dexra s1 is also expressed in other pituitary cells than corticotropes. Copyright (C) 2001 S. Karger AG, Basel.