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Glucocorticoid Control of Rat Growth Hormone Gene Expression: Effect on Cytoplasmic Messenger Ribonucleic Acid Production and Degradation

Metabolic Research Unit and the Departments of Medicine, Biochemistry, and Biophysics, University of California San Francisco, California 94143

Address requests for reprints to: Barry J. Gertz, M.D., Ph.D., Merck Sharp & Dohme Research Laboratories, P.O. Box 2000, WB D-242, Rahway, New Jersey 07065-0914.

Abstract

The effect of the glucocorticoid dexamethasone on the production and degradation of rat GH (rGH) cytoplasmic mRNA was studied in cultured rat pituitary tumor (GC) cells. The incorporation of [³H]uridine into both rGH cytoplasmic mRNA and the pyrimidine nucleotide precursor pool was determined in hormone-treated and control cells. From these measurements glucocorticoid effects on absolute production rates of rGH cytoplasmic mRNA were determined and compared to effects on rGH mRNA accumulation. Rat GH mRNA half-life was then calculated based on a first-order decay model. Rat GH mRNA half-life was also directly assayed by: 1) pulse-chase studies and 2) measuring the kinetics of decay of rGH mRNA in cells after transfer from serum-containing to hormone-deficient media. From these independent analyses rGH mRNA half-life estimates ranged from 28–55 h in different experiments. Within individual experiments there was little variability of rGH mRNA decay rates; glucocorticoids were found not to alter the stability of rGH cytoplasmic mRNA. Glucocorticoid induction of rGH cytoplasmic mRNA accumulation was accounted for solely on the basis of increased mRNA production.

FOOTNOTES

This research was supported by Grant AM-19997 from the National Institutes of Health and a gift from California Biotechnology, Inc.

^* Supported by a National Research Service Award from the NIH and a Junior Faculty Research Award from the American Cancer Society. Present address is Merck, Sharp & Dohme Research Laboratories, P.O. Box 2000, Rahway, NJ 07065.

Received for publication September 8, 1987. Accepted for publication October 15, 1987.

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