Editorial: Did Eucaryotic Steroid Receptors Evolve from Intracrine Gene Regulators?*

作者：Bert W. O’Malley · 发表于：Endocrinology · 年份：1989 · DOI：10.1210/endo-125-3-1119 · 被引用次数：68 · 研究领域：Steroid Chemistry and Biochemistry

It is likely that evolution of the steroid receptor superfamily of gene regulators began a thousand million years ago in very primitive organisms. Such organisms would have lacked cellular specialization (glands) and an endocrine system as such. Their needs were simple: 1) to survive in the environment and 2) to replicate. They were dependent on their environment for metabolic substrates and energy sources. Their prime regulatory need was to control their own metabolism. Classical steroid hormones were nonexistent. Although admittedly hypothetical, I suggest the following evolutionary scenario. Primitive members of the steroid receptor superfamily were intracellular receptors which bound environmental nutritional agents and/or metabolic substrates (e.g. amino acids or sugars) and by-products as ligands. These ligands were nonsteroidal in nature, with the possible exception of cholesterol. It is not inconceivable that certain of these intracellular receptors were activated by amino acids or other peptides. The ligands were likely to be absorbed from the environment or produced within the same cells which contained these receptors, thereby providing apparent constitutive activity. An exception would be times of metabolic deprivation when endogenous ligand concentration may have dropped. In this case the receptors would have become inactivated and gene expression shut down. Under normal conditions, however, the ligand pools would be used to modulate metabolic pathways and contro...