The origins of intracrine hormone action

A growing number of peptide hormones and growth factors have been shown to operate in the intracellular space after either internalization or retention in their cells of synthesis. These factors, called intracrines, in many cases are expressed as multiple isoforms, traffic to nucleus or nucleolus, and regulate gene transcription. Some intracrines are angiogenic. It is here argued that intracrine action is the modern analogue of a biologically ancient mechanism for regulating message translation and ribosome synthesis. The implications of this view for research and therapeutics are discussed.