Glucocorticoids regulate the expression of a rat growth hormone gene lacking 5' flanking sequences.

Abstract

Rat growth hormone (rGH) gene expression is regulated by glucocorticoids in vivo and in cultured pituitary cells. After the co-transfer of a plasmid containing the rGH gene into mouse L-cells (with or without the simian virus 40 enhancer), little or no normal rGH mRNA is produced. Instead, the predominant rGH gene transcripts are about 0.75 kilobase pairs (kb); these lack the first two exons of the rGH but possess a 3' end that terminates accurately. Nevertheless, the levels of these transcripts are increased by glucocorticoids. When all of the rat sequences 5' to an Xho1 site located 7 nucleotides downstream from the rGH gene physiological cap site are deleted and the mutant gene introduced into L-cells, the transfectant cell lines still produce the 0.75-kb transcripts; however, in addition, these cells produce a more abundant 1.1-kb mRNA that has a 3' terminus similar to that of rGH mRNA, but whose 5' termini begin in the region of, but not at, the initiation site used in pituitary cells. Both of these transcripts are increased 3- to 5-fold by 1 microM concentration of the glucocorticoid dexamethasone. These data indicate that 1) deletion of all of the rGH gene 5' flanking sequences allows formation of approximately full length transcripts and 2) sequences containing information for regulation of rGH gene expression in L-cells by glucocorticoids are contained in the structural portion of the gene and/or the 3' flanking sequence.