Epoxyeicosatrienoic acids (EETs): A novel class of second messengers of hormonal functional responses

Epoxyeicosatrienoic acids (EETs) are a class of cytochrome P450 (P450) arachidonic acid (AA) metabolites with diverse biological activities including anti-hypertensive, vasodilatory, angiogenic, and anti-inflammatory properties. While their functions as autocrine and paracrine mediators in cardiovascular and renal systems are well established, their mechanism of action and roles in hormonal functional responses are yet to be fully defined. In this review, we highlight extant evidence of their participation in hormonal transmembrane signal transduction leading to the activation of the ERK1/2 or Akt serine/threonine kinases. Based on studies with EGF (Epidermal Growth Factor), VEGF (Vascular Endothelial Growth Factor) and insulin binding to their membrane bound receptors, we propose to include EETs to the inventory of intracellular mediators associated with the functional responses elicited upon selected hormone/receptor interactions. •Epoxyeicosatrienoic acids (EETs) are second messengers of hormonal signaling.•Hormones activate EET biosynthesis and/or release from membrane stores.•EETs activate kinases to mediate downstream effects.