Regulation of the 5'-flanking Region of the Mouse Androgen Receptor Gene by cAMP and Androgen

Mol Endocrinol. 1993 Dec;7(12):1530-40. doi: 10.1210/mend.7.12.7511785.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Androgens / physiology*
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Colforsin / pharmacology
  • Coturnix
  • Cyclic AMP / physiology*
  • Dihydrotestosterone / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects*
  • Genes
  • Mice
  • Molecular Sequence Data
  • Pituitary Gland, Anterior / drug effects
  • Pituitary Gland, Anterior / metabolism
  • Promoter Regions, Genetic
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Regulatory Sequences, Nucleic Acid
  • Sequence Deletion

Substances

  • Androgens
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Dihydrotestosterone
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Cyclic AMP
  • 1-Methyl-3-isobutylxanthine