Estrogens are the key hormones regulating the development
and function of reproductive organs in all vertebrates. Recent
evidence indicates that estrogens play important roles in the
immune system, cancer development, and other critical
biological processes related to human well-being. Obviously,
the gonads (ovary and testis) are the primary sites of estrogen
synthesis, but estrogens synthesized in extra- gonadal sites
play an equally important role in controlling biological
activities. Understanding non-gonadal sites of estrogen
synthesis and function is crucial and will lead to therapeutic
interventions targeting estrogen signaling in disease prevention
and treatment. Developing a rationale targeting strategy
remains challenging because knowledge of extra-gonadal
biosynthesis of estrogens, and the mechanism by which
estrogen activity is exerted, is very limited. In this review, we
will summarize recent discoveries of extra-gonadal sites of
estrogen biosynthesis and their local functions and discuss the
significance of the most recent novel discovery of intestinal
estrogen biosynthesis. [BMB Reports 2016; 49(9): 488-496]