Expanding the structural footprint of xenoestrogens

Abstract

Many synthetic chemicals with structural similarity to estradiol bind to the estrogen receptor and disrupt the normal estrogen physiology in humans and other vertebrates. Most of these xenoestrogens contain a structure that mimics the phenolic A ring on E2. This phenolic A ring is a defining property of E2 that distinguishes it from aldosterone, cortisol, progesterone and testosterone. However, Δ5-androstenediol, 5a-androstanediol and 27-hydroxycholesterol also have estrogenic activity, despite having important structural differences in their A rings compared to E2. Unlike E2, these steroids have a saturated A ring with a 3β-hydroxyl and a C19 methyl group. An implication of their estrogenic activity is that synthetic chemicals containing a saturated A ring with a 3b-hydroxyl and a C19 methyl group are potential xenoestrogens.