Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.25 (MEKK1)
 1,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the possible involvement of mitogen-activated protein (MAP) kinase activation in the secretory process and gene expression of prolactin and growth hormone. Thyrotropin-releasing hormone (TRH) rapidly stimulated the secretion of both prolactin and growth hormone from GH3 cells. Secretion induced by TRH was not inhibited by 50 microM PD098059, but was completely inhibited by 1 microM wortmannin and 10 microM KN93, suggesting that MAP kinase does not mediate the secretory process. Stimulation of GH3 cells with TRH significantly increased the mRNA level of prolactin, whereas expression of growth hormone mRNA was largely attenuated. The increase in prolactin mRNA stimulated by TRH was inhibited by addition of PD098059, and the decrease in growth hormone mRNA was also inhibited by PD098059. Transfection of the cells with a pFC-MEKK vector (a constitutively active MAP kinase kinase kinase), significantly increased the synthesis of prolactin and decreased the synthesis of growth hormone. These data taken together indicate that MAP kinase mediates TRH-induced regulation of prolactin and growth hormone gene expression. Reporter gene assays showed that prolactin promoter activity was increased by TRH and was completely inhibited by addition of PD098059, but that the promoter activity of growth hormone was unchanged by TRH. These results suggest that TRH stimulates both prolactin and growth hormone secretion, but that the gene expressions of prolactin and growth hormone are differentially regulated by TRH and are mediated by different mechanisms.
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PMID:Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role for mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells. 1208 5

We examined the effects of sex steroids on prolactin promoter activity in rat somatolactotrophic GH3 cells. Both estradiol (E2) and progesterone (P4) were found to inhibit basal prolactin promoter activity, but to potentiate Thyrotropin-releasing hormone (TRH)-induced prolactin promoter activity. P4 had a greater inhibitory effect on basal prolactin promoter activity than E2, and P4 also potentiated TRH-induced prolactin promoter more potently than E2. Combined treatment with E2 and P4 further increased TRH-induced prolactin promoter activity. E2 and P4 also both reduced basal serum response element (SRE) promoter activity, and increased TRH-induced SRE promoter activity. Combination treatment with E2 and P4 reduced basal activity of SRE promoter and increased TRH-induced SRE activity more potently than E2 or P4 alone. In contrast, basal cAMP response element (CRE) promoter activity was not influenced by either E2 or P4, although TRH-induced CRE promoter was potentiated by each of these steroids, and was further increased by E2 and P4 combination treatment. Both E2 and P4 increased TRH-induced extracellular signal-regulated kinase (ERK) phosphorylation; however, intracellular cAMP levels was not influenced by E2 or P4. TRH-induced CRE promoter was inhibited by mitogen-activated protein kinase/ERK kinase (MEK) inhibitor and was increased by overexpression of MEK kinase (MEKK). This study showed that ERK and SRE transcriptional pathways, but not the cAMP/CRE pathway, may be involved in the suppression of basal prolactin promoter activity, whereas both the ERK/SRE and MAP kinase-mediated CRE pathways appear to be involved in the increased transcriptional efficiency of the prolactin promoter induced by TRH stimulation.
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PMID:Effects of estradiol and progesterone on prolactin transcriptional activity in somatolactotrophic cells. 2278 35