Glucocorticoid-induced proteins in rat thymus cells

Area of Science:

• Cellular biology
• Molecular endocrinology
• Biochemistry

Background:

• Glucocorticoids induce rapid metabolic suppressions in rat thymus cells.
• The precise molecular events initiating these suppressions are not fully understood.

Purpose of the Study:

• To investigate if hormone-induced changes in individual protein synthesis initiate glucocorticoid-induced metabolic suppressions.
• To identify specific proteins whose synthesis is rapidly altered by dexamethasone.

Main Methods:

• Screening of approximately 2500 individual protein synthesis rates using giant two-dimensional gel electrophoresis.
• Treatment of rat thymus cells with dexamethasone and cordycepin (an mRNA processing inhibitor).
• Analysis of protein synthesis rates and subcellular localization.

Main Results:

• Dexamethasone rapidly increased the synthesis rates of at least six proteins within 15-45 minutes.
• These early changes in protein synthesis correlate with hormone-induced inhibition of glucose transport.
• Later changes in two proteins paralleled decreased mitochondrial ATP production and increased nuclear fragility.
• Cordycepin blocked dexamethasone-induced protein labeling and selectively inhibited synthesis of early induced proteins, indicating short mRNA half-lives.
• Two induced proteins were found in plasma and nuclear membrane fractions.

Conclusions:

• Rapidly induced proteins with short-lived mRNAs may act as key regulators in glucocorticoid signaling.
• These findings provide insights into the molecular mechanisms underlying rapid hormonal responses in thymus cells.