Evolution of steroid receptors from an estrogen-sensitive ancestral receptor

Mol Cell Endocrinol. 2011 Mar 1;334(1-2):31-8. doi: 10.1016/j.mce.2010.09.003. Epub 2010 Sep 15.

Abstract

Members of the steroid hormone receptor (SR) family activate transcription from different DNA response elements and are regulated by distinct hormonal ligands. Understanding the evolutionary process by which this diversity arose can provide insight into how and why SRs function as they do. Here we review the characteristics of the ancient receptor protein from which the SR family descends by a process of gene duplication and divergence. Several orthogonal lines of evidence - bioinformatic, phylogenetic, and experimental - indicate that this ancient SR had the capacity to activate transcription from DNA estrogen response elements in response to estrogens. Duplication and divergence of the ancestral SR gene subsequently generated new receptors that were activated by other steroid hormones, including progestagens, androgens, and corticosteroids. The androgen and progesterone receptors recruited as their ligands steroids that were previously present as biochemical intermediates in the synthesis of estrogens. This process is an example of molecular exploitation--the evolution of new molecular interactions when an older molecule, which previously had a different function, is co-opted as a binding partner by a newly evolved molecule. The primordial interaction between the ancestral steroid receptor and estrogens may itself have evolved due to an early molecular exploitation event.

Publication types

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

MeSH terms

  • Androgens / metabolism
  • Animals
  • DNA / metabolism
  • Estrogens / metabolism*
  • Evolution, Molecular*
  • Gene Duplication
  • Gene Expression
  • Gonadal Steroid Hormones / metabolism*
  • Humans
  • Ligands
  • Models, Biological
  • Phylogeny
  • Protein Binding
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Response Elements / genetics
  • Steroids / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Androgens
  • Estrogens
  • Gonadal Steroid Hormones
  • Ligands
  • Receptors, Androgen
  • Receptors, Estrogen
  • Steroids
  • Transcription Factors
  • DNA