Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain

Cell. 1988 Mar 11;52(5):685-95. doi: 10.1016/0092-8674(88)90406-0.

Abstract

Prolactin gene expression is negatively regulated by glucocorticoids, and by estrogens when positive estrogen regulatory elements in the prolactin gene are removed. Mutational analysis of estrogen receptor confirms that inhibition is a function of receptor, and that transcriptional activation and inhibition require distinct, separable structural elements. Inhibition is dependent on a 63 amino acid region (amino acids 251-314) distinct from the DNA-binding and steroid-binding domains. The comparable region of glucocorticoid receptor confers inhibitory actions on a hybrid receptor. Multiple, nonoverlapping sequences in the rat prolactin 5'-flanking genomic region that confer inhibition by both steroid hormones contain related cis-active elements that bind a common, tissue-specific positive transcription factor, called Pit-1. Experimental results indicate that positive and negative transcriptional effects of estrogen receptor are mediated by separate functional domains, and suggest the protein-protein interactions between steroid hormone receptors and other transcription factor(s) mediate inhibition.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA / metabolism*
  • DNA, Recombinant
  • Estrogens / pharmacology
  • Gene Expression Regulation* / drug effects
  • Glucocorticoids / pharmacology
  • Molecular Sequence Data
  • Mutation
  • Pituitary Gland / metabolism
  • Prolactin / genetics*
  • Rats
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / physiology*
  • Regulatory Sequences, Nucleic Acid
  • Structure-Activity Relationship
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Transfection

Substances

  • DNA, Recombinant
  • Estrogens
  • Glucocorticoids
  • Receptors, Estrogen
  • Transcription Factors
  • Prolactin
  • DNA