Regulation of the 5'-flanking region of the mouse androgen receptor gene by cAMP and androgen

Jonathan Lindzey, Mike Grossmann, M. Vijay Kumar, Donald J. Tindall

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Both androgens and cAMP-mediated hormones are known to regulate expression of the androgen receptor (AR) gene. In order to determine whether these effects occur at the transcriptional level, transfection studies were conducted with a 1.5-kilobase fragment of the 5'-flanking region of the mouse AR gene coupled to a chloramphenicol acetyltransferase (CAT) reporter gene. We demonstrated that the cAMP pathway regulates expression of the mouse AR (mAR) 5'-CAT construct in mouse pituitary (alpha T3-1), rat pituitary (GC), and quail fibroblast (QT6) cell lines. Deletional analysis indicated that several areas of this clone, including a region containing a putative cAMP response element (CRE), are involved in mediating cAMP regulation of the AR gene. Oligonucleotides containing a putative CRE, linked to the thymidine kinase promoter of pBLCAT2, conferred increased forskolin induction of CAT activity. Furthermore, overexpression of a CRE binding protein up-regulated expression of the mAR 5'-CAT constructs. Bandshift data demonstrated that the putative CRE forms specific, competable complexes with nuclear proteins from alpha T3-1 and QT6 cells. Additional experiments indicated that AR can modulate both basal and forskolin-induced CAT activity in an androgen-dependent fashion. These data provide evidence that the 5'-flanking region of the mAR gene contains sequences which mediate the effects of both cAMP and androgens.

Original languageEnglish (US)
Pages (from-to)1530-1540
Number of pages11
JournalMolecular Endocrinology
Volume7
Issue number12
DOIs
StatePublished - Dec 1993

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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