Regulation of steroidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells.

Abstract

The regulation of steroidogenic acute regulatory protein (StAR) gene expression and the synthesis of steroids from cholesterol in ectopic endometriosis tissues were investigated. Peritoneal fluid and endometrial tissues were collected from patients with endometriosis and otherwise healthy women. Peritoneal progesterone and 17 beta-E2 concentrations were highest in early stage endometriosis compared with those in advanced stage endometriosis and in normal women. In concordance with the profile of peritoneal steroids, StAR mRNA and protein were greatest in ectopic implants of early endometriosis. In the advanced stage, concentrations of StAR mRNA and protein were also greater compared with those in normal endometrium. In contrast, P450 side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase transcripts were not different between normal endometrium and ectopic endometriotic implants. Expression of StAR mRNA was detected in purified stromal, but not epithelial, cells. Treatment with PGE(2), but not TNF alpha, or IL-1 beta significantly increased StAR expression and thus induced progesterone production in cultured endometriotic stromal cells. These results demonstrated that aberrant expression of StAR in ectopic endometriotic tissues leading to increased peritoneal progesterone is associated with the formation of endometriosis. Induction of StAR gene expression by peritoneal PGE(2) in endometriotic stromal cells may further contribute to the development of endometriosis.