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Regulation of Dexras1 expression by endogenous steroids
M D Brogan1, E N Behrend, R J Kemppainen
1Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
Abstract:
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 of Dexras1 is unknown, but its rapid induction in response to glucocorticoids suggests the possibility that it may be involved in negative feedback regulation of corticotropin secretion. To better understand the control of Dexras1 expression, possible effects of other steroid hormones on its expression 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 induced 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 injection of glucocorticoids, induced Dexras1 expression in mouse pituitary. Other steroids were without effect. The results suggest that in AtT-20 corticotropes, Dexras1 expression is only induced by glucocorticoid-type steroids. In pituitary glands of mice, the gene's expression is also responsive to E(2). We conclude that either Dexras1 expression in corticotropes from normal mice is regulated differently from that in AtT-20 cells, or that Dexras1 is also expressed in other pituitary cells than corticotropes.
Insights
Dexras1 gene expression is induced by glucocorticoids in AtT-20 cells. However, in mouse pituitaries, both glucocorticoids and beta-estradiol (E2) stimulate Dexras1 expression, suggesting differential regulation.
Area of Science:
- Molecular endocrinology
- Gene expression regulation
- Steroid hormone signaling
Background:
- Dexras1, a novel Ras superfamily protein, is rapidly induced by glucocorticoids in AtT-20 corticotrope cells.
- Its function remains unknown, but induction suggests a role in negative feedback of corticotropin secretion.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling Dexras1 gene expression.
- To determine the effects of various steroid hormones on Dexras1 expression in AtT-20 cells and mouse pituitaries.
Main Methods:
- Treatment of AtT-20 cells and mice with six different steroids: aldosterone, corticosterone, dexamethasone, beta-estradiol, progesterone, and testosterone.
- Assessment of Dexras1 expression using reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis.
Main Results:
- In AtT-20 cells, only glucocorticoids (dexamethasone and corticosterone) induced Dexras1 expression.
- In mouse pituitaries, both glucocorticoids and beta-estradiol (E2) significantly increased Dexras1 expression.
- Other tested steroids had no effect on Dexras1 expression in either model.
Conclusions:
- Dexras1 expression in AtT-20 corticotropes is primarily regulated by glucocorticoids.
- Dexras1 expression in the mouse pituitary gland is also responsive to beta-estradiol (E2).
- These findings suggest differential regulation of Dexras1 expression between AtT-20 cells and mouse pituitary, potentially involving cell-specific mechanisms or expression in non-corticotrope pituitary cells.