title: 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.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane Medical University, Izumo 693-8501, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kanasaki
authors.forename: Toshie
authors.initials: T
authors.lastname: Yonehara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Eishichi
authors.initials: E
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D013006:Growth Hormone / Q000096:biosynthesis; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010907:Pituitary Hormones / Q000096:biosynthesis / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011388:Prolactin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D010907:Pituitary Hormones; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013006:Growth Hormone; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one