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Glucocorticoid-mediated induction of glucocortin: a rapid primary response common to major target tissues
Abstract:
Glucocorticoids are known to rapidly induce four proteins in rat thymus cells in time to account for the earliest known metabolic hormone effects. We report here an additional protein, which we refer to as "glucocortin" (Mr = 17,000, pI = 4.7). It is of special interest since it is the only protein rapidly induced in all of the glucocorticoid target cells we have examined. We have characterized the kinetics of glucocortin mRNA induction in isolated thymus cells. Giant two-dimensional gel electrophoretic analysis of in vitro translation products reveals a 2-fold increase in the level of translatable mRNA within 15 min of dexamethasone addition, with maximal stimulation (approximately equal to 7-fold) by 45 min. Cycloheximide does not reduce the hormone-mediated increase in glucocortin mRNA, suggesting that the induction represents a primary response to glucocorticoids. This protein is induced by dexamethasone in a dose-dependent manner, with maximal induction at 10(-6) M and partial inductions at concentrations as low as 10(-10) M. It is strongly induced by cortisol at 10(-6) M, but it is not induced by estradiol or testosterone or by thyroid hormone, even at concentrations as high as 10(-6) M. Deoxycorticosterone has no effect at 10(-8) M but does generate a half-maximal effect at 10(-6) M, a finding consistent with its status as a partial glucocorticoid agonist. In summary, glucocortin appears to be a primary glucocorticoid-induced protein that represents the most rapid induction so far detected, and it appears to be the only one that may be common to all glucocorticoid target cells.
Insights
Researchers discovered a new protein, glucocortin, rapidly induced by glucocorticoids in all target cells. This protein represents a primary response to glucocorticoids and may be common to all cells affected by these hormones.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Glucocorticoids are potent metabolic hormones known for rapid effects.
- Existing research identifies four proteins rapidly induced by glucocorticoids in rat thymus cells.
- The precise molecular mechanisms and common cellular responses to glucocorticoids require further elucidation.
Purpose of the Study:
- To identify and characterize novel proteins rapidly induced by glucocorticoids.
- To investigate the kinetics and specificity of glucocortin induction in target cells.
- To determine if glucocortin represents a primary, common response to glucocorticoid signaling.
Main Methods:
- Two-dimensional gel electrophoresis of in vitro translation products.
- Analysis of messenger RNA (mRNA) induction kinetics using cycloheximide.
- Dose-response studies with various steroid hormones including dexamethasone, cortisol, and deoxycorticosterone.
Main Results:
- A novel protein, "glucocortin" (Mr = 17,000, pI = 4.7), was identified.
- Glucocortin mRNA levels increased 2-fold within 15 minutes and 7-fold by 45 minutes after dexamethasone addition.
- Glucocortin induction was observed in all examined glucocorticoid target cells, dose-dependently induced by dexamethasone and cortisol, but not by other steroid or thyroid hormones.
Conclusions:
- Glucocortin is a primary glucocorticoid-induced protein, representing the fastest hormone induction reported to date.
- Glucocortin may be the sole protein rapidly induced in all glucocorticoid target cells.
- This finding offers new insights into the fundamental mechanisms of glucocorticoid action.