Adrenal and sex steroid receptor evolution: environmental implications

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Endocrinology

Background:

• Nuclear receptors bind diverse ligands like steroids and retinoids.
• Adrenal and sex steroid receptors form a distinct evolutionary clade.
• Their precise ancestral relationships remain incompletely understood.

Purpose of the Study:

• To resolve the evolutionary phylogeny of adrenal and sex steroid receptors.
• To investigate the relationship between sequence divergence and steroid specificity.
• To understand the evolutionary origins and changes in these receptors.

Main Methods:

• Comparative sequence analysis of fish and mammalian steroid receptors.
• Phylogenetic reconstruction of nuclear receptor evolution.
• Analysis of hormone-binding domain sequence divergence.

Main Results:

• Estrogen receptor identified as the most ancient vertebrate steroid receptor.
• Adrenal and sex steroid receptors likely originated in jawless fish or protochordates.
• Sequence divergence correlates with altered steroid specificity, impacting xenobiotic evaluation.
• Retinoid X receptor clade is evolutionarily closest to adrenal/sex steroid receptors.

Conclusions:

• Evolution of adrenal and sex steroid receptors involved modifications in protein-protein interactions and ligand recognition.
• Phylogenetic context is crucial for interpreting endocrine effects of xenobiotics.
• Adrenal and sex steroid receptors function as homodimers, unlike Retinoid X receptors which form heterodimers.