REGULATED EXPRESSION OF THE HUMAN CORTICOTROPIN RELEASING HORMONE GENE BY CYCLIC-AMP

被引:51
作者
ADLER, GK
SMAS, CM
FIANDACA, M
FRIM, DM
MAJZOUB, JA
机构
[1] HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV ENDOCRINOL,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DEPT NEUROBIOL,PROGRAM NEUROSCI,BOSTON,MA 02115
关键词
Corticotropin-releasing hormone; Cyclic AMP; mRNA; Transcriptional start site;
D O I
10.1016/0303-7207(90)90156-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The factors controlling the expression of the hypothalamic neuropeptide, corticotropin releasing hormone (CRH), are poorly understood. We have used a mouse anterior pituitary cell line, AtT-20, permanently transfected with the human CRH gene as a model for studying the regulation of the CRH gene by cyclic AMP. Previously, we demonstrated that in this system the CRH gene is correctly expressed and appropriately negatively regulated by glucocorticoids. Treatment of five CRH-producing cell lines with an activator of adenylate cyclase (forskolin, 0.1-50 μM for 24 h) caused a dose-dependent and specific increase in the amount of CRH mRNA and radioimmunoassay-detectable CRH peptide secreted into the medium. Ribonuclease protection analysis revealed that the CRH gene was transcribed from multiple transcriptional initiation sites located over several hundred nucleotides. Forskolin treatment resulted in a specific increase in the CRH mRNA transcripts initiating from one of these many transcriptional start sites. © 1990.
引用
收藏
页码:165 / 174
页数:10
相关论文
共 32 条
[1]  
ADLER GK, 1988, J BIOL CHEM, V263, P5846
[2]  
BIRNBOIM HC, 1979, NUCLEIC ACIDS RES, V7, P1513
[3]   MULTIHORMONAL REGULATION OF THE HUMAN, RAT, AND BOVINE GROWTH-HORMONE PROMOTERS - DIFFERENTIAL-EFFECTS OF 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE, THYROID-HORMONE, AND GLUCOCORTICOIDS [J].
BRENT, GA ;
HARNEY, JW ;
MOORE, DD ;
LARSEN, PR .
MOLECULAR ENDOCRINOLOGY, 1988, 2 (09) :792-798
[4]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[5]  
EMANUEL RL, 1989, CLIN RES, V37, pA357
[6]   CHARACTERIZATION AND GESTATIONAL REGULATION OF CORTICOTROPIN-RELEASING HORMONE MESSENGER-RNA IN HUMAN-PLACENTA [J].
FRIM, DM ;
EMANUEL, RL ;
ROBINSON, BG ;
SMAS, CM ;
ADLER, GK ;
MAJZOUB, JA .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (01) :287-292
[7]   ALTERNATIVE SITES OF TRANSCRIPTION INITIATION UPSTREAM OF THE CANONICAL CAP SITE IN HUMAN GAMMA-GLOBIN AND BETA-GLOBIN GENES [J].
GRINDLAY, GJ ;
LANYON, WG ;
ALLAN, M ;
PAUL, J .
NUCLEIC ACIDS RESEARCH, 1984, 12 (04) :1811-1820
[8]   AN ESCHERICHIA-COLI PROMOTER THAT REGULATES TRANSCRIPTION BY DNA SUPERHELIX-INDUCED CRUCIFORM EXTRUSION [J].
HORWITZ, MSZ ;
LOEB, LA .
SCIENCE, 1988, 241 (4866) :703-705
[9]   INTERACTIONS BETWEEN THE HORMONE-SENSITIVE ADENYLATE-CYCLASE SYSTEM AND THE PHOSPHOINOSITIDE-METABOLIZING PATHWAY IN HUMAN-PLATELETS [J].
JAKOBS, KH ;
WATANABE, Y ;
BAUER, S .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1986, 8 :S61-S64
[10]  
JAMESON JL, 1986, ENDOCRINOLOGY, V119, P2560