Figure 1: A schematic demonstration depicted the estrogen biosynthesis and its regulation in endometriosis. A full complete set of steroidogenic enzymes expressed in endometriotic tissues. In the endometriotic stromal cells, cholesterol is de novo converted to E2 by six enzymes, namely StAR, P450scc, HSD3B2, P450c17, P450arom, and HSD17B1. The inflammatory substances can induce the expression of COX-2, which catalyzes AA to synthesis of PGE2 in endometriotic stromal cells. PGE2, through binding to and subsequently activation of EP2 or EP4, can activate the PKA signaling pathway via raising the intracellular levels of cAMP, which could enhance binding of SF-1 and CREB to promoters of steroidogenic genes to promote E2 synthesis in endometriotic stromal cells. High levels of local E2 (through ER-β) and PGE2 in turn to induce COX-2 expression, which results in overexpression of steroidogenic genes, overexpression of COX-2, and continuous local production of E2 and PGE2 in endometriotic tissue. HSD17B2, expressed in epithelial cells, is the main enzyme for metalizing E2 to E1 in endometriotic tissue. Progesterone induces the expression of epithelial HSD17B2 by activating stromal PR-B, which can mediate the formation of RA to bind to the promoter and thus activation of HSD17B2. In endometriotic tissue, the decreased PR-B levels in the stromal cell disrupt the paracrine action of progesterone. ER-β suppresses ER-α and PR-B, leading to progesterone resistance and deficient inactivation of E2 in endometriotic tissue.[6,28] AA: Arachidonic acid; PGE2: Prostaglandin E2; RA: Retinoic acid; COX-2: Cyclooxygenase-2; A: Androstenedione; E1: Estrone; E2: Estradiol; SF-1: Steroidogenic factor-1; CREB: cAMP-response element-binding protein; StAR: Steroidogenic acute regulatory; P450scc: Cytochrome P450 side-chain cleavage; HSD3B2: 3-hydroxysteroid dehydrogenase type 2; P450c17: Cytochrome P450 17a-hydroxylase/17, 20-lyase; HSD17B1: 17 beta-hydroxysteroid dehydrogenase type 1; HSD17B 2: 17 beta-hydroxysteroid dehydrogenase type 2; PKA: Protein kinase A; ER-α: Estrogen receptor-α; ER-β: Estrogen receptor-β.