Glucocorticoids enhance stability of human growth hormone mRNA.

Abstract

We have studied the control of expression of the human growth hormone (hGH) Steroid hormones regulate gene expression by associating with receptor proteins which then interact with specific DNA sequences in the chromosome (for a review, see reference 60). The glucocorticoid receptor, for example, binds to specific sites in several hormone-responsive genes, and this interaction presumably results in enhanced transcription upon exposure to glucocorticoid hormones (for reviews, see references 41 and 59). However, the effects of steroid hormones on gene expression are not restricted to transcriptional events (6,20,35,51). Estrogen, for example, results in a 1,000-fold increase in the transcription of the viteilogenin gene in Xenopus laevis liver but also exerts a profound effect on the stability of vitellogenin mRNA (6). Given the specificity with which estrogen enhances the stability of vitellogenin mRNA, it is likely that sequences reside within this mRNA which are responsive to the hormone and increase the expression of this gene via posttranscriptional mechanisms.Expression of the growth hormone (GH) genes is restricted to somatotrophs of the anterior pituitary (26) and is regulated by the hypothalamic growth hormone releasing factor (3, 4, 22) and glucocorticoid and thyroid hormones.'In cultures of rat pituitary cells (GH3 and GC [2, 61]), either glucocorticoid or thyroid hormone increases the level of the GH mRNAs and a synergism is observed when these two hormones are added together (32,45,47,50,53). Thyroid hormone increases the rate of transcription of the rat GH gene in pituitary cell lines (12,14,19,38,49,58), and the regulatory element responsive to thyroid hormone has been identified within the 5' flanking sequences of the rat GH gene (8,12 However, the level of transcriptional activation in the presence of glucocorticoids observed in vitro in nuclear transcription assays is significantly lower than the steady-state level of induction of GH mRNA in the rat pituitary cells, suggesting that posttranscriptional events, mediated by steroids, may also be operative (49).In previous studies, we have introduced the human GH (hGH) gene into murine fibroblasts and demonstrated that hGH mRNA is inducible by glucocorticoids (42). To localize the sequences responsible for induction and to determine the mechanism by which these cis-acting sequences enhance gene expression, we have now constructed a series of fusion genes between hGH and the herpes simplex virus (HSV) thymidine kinase (tk) gene. We observed that a gene consisting of hGH cDNA sequences, driven by a tk promoter and flanked by 3' tk DNA, is inducible in transformed fibroblasts. Further, this induction results at least in part from changes in mRNA stability, suggesting that glucocorticoids regulate hGH expression at the level of RNA stability as well as RNA synthesis. MATERIALS AND METHODSCell culture and hormonal induction. Mouse Ltk-aprtcells were maintained as described previously (56), and Ltkaprt+ transformants were selected and mnaintained in Dulb...

Degradation of cellular mRNA during influenza virus infection: its possible role in protein synthesis shutoff

“…Therefore, it is proposed that infection with influenza virus induces a specific degradation of cellular m R N A s . (Huez et al, 1978;Mercer & Wake, 1985;Paek & Axel, 1987;reviewed in Bernstein & Ross, 1989;Braverman, 1989). In turn, the stability of the poly(A) tract appears to be related to its interaction with the poly(A)-binding protein (PABP), which would increase its resistance to nucleases .…”

Relationship between Yeast Polyribosomes and Upf Proteins Required for Nonsense mRNA Decay

“…The notion of a global pathway for eukaryotic mRNA decay suggested by early work in animal cells has recently been greatly advanced by studies in the yeast Saccharomyces cerevisiae (1)(2)(3)(4). Using an in vivo transcriptional pulse, the temporal fate of newly synthesized mRNA was established by monitoring poly(A) tail length, loss of the m 7 Gppp cap, disappearance of the mRNA, and the appearance of degradation intermediates.…”

Regulation of GH-Releasing Hormone Receptors

“…Figure 5 shows the effects of adrenalectomy on pituitary GRH receptor mRNA levels in rats. GRH receptor mRNA levels were significantly decreased 3 days after adrenalectomy, [13,14]. In the present study, stimulatory actions of Dex in GRH receptor mRNA levels were delayed, requiring more than 2 h at least.…”