Figure 2.

Role of estrogen in leiomyoma pathogenesis. Although leiomyomas are exposed to circulating estrogens from the ovary, it appears that substantial amounts of estrogen are also produced in situ via aromatization of androgens from the adrenal gland and ovary. The biologically active estrogen, estradiol, acts primarily through ERα to induce transcription of genes involved in proliferation and ECM formation, but its principal function is up-regulation of PR expression, thereby increasing leiomyoma responsiveness to progesterone. Aromatase inhibitors effectively block the in situ production of estradiol, thus decreasing leiomyoma responsiveness to both estrogen and progesterone signaling.