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2009•Molecular EndocrinologyOpen access

Prostaglandin E2 via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis

Erkut Attar, Hideki Tokunaga, Gonca İmir, Mehmet Bertan Yılmaz, David Byron Redwine, Michael Putman, Bilgin Gürateş, Rükset Attar, Nobuo Yaegashi, Dale Buchanan Hales, Serdar Ekrem Bulun

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Abstract

Products of at least five specific steroidogenic genes, including steroidogenic acute regulatory protein (StAR), which facilitates the initial entry of cytosolic cholesterol into the mitochondrion, side-chain-cleavage enzyme (P450scc), 3β-hydroxy-steroid-dehydrogenase-2 (HSD3B2), 17-hydroxylase/17–20-lyase (P450c17) and aromatase which catalyzes the final step, are necessary for the conversion of cholesterol to estrogen. Expression and biologic activity StAR and aromatase were previously demonstrated in endometriosis but not in normal endometrium. PGE2 induces aromatase expression via the transcriptional factor steroidogenic factor-1 (SF1) in endometriosis, which is opposed by chicken-ovalbumin upstream-transcription factor (COUP-TF) and Wilms’ tumor-1 (WT1) in endometrium. To demonstrate a complete steroidogenic pathway leading to estrogen biosynthesis in endometriotic cells and the transcriptional mechanisms that regulate basal and PGE2-stimulated estrogen production in endometriotic cells and endometrium. Compared with normal endometrial tissues, expression of StAR, P450scc, HSD3B2 P450c17, aromatase and SF1 were significantly higher in endometriotic tissues. PGE2 induced the expression of all steroidogenic genes, production of progesterone, estrone and estradiol, and StAR promoter activity in endometriotic cells. Overexpression of SF1 induced, whereas COUP-TFII or WT1 suppressed, StAR promoter activity. PGE2 induced coordinate binding of SF1 to StAR and aromatase promoters, but decreased COUP-TFII binding in endometriotic cells. COUP-TFII or WT1 binding to both promoters was significantly higher in endometrial compared with endometriotic cells. Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.

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Products of at least five specific steroidogenic genes, including steroidogenic acute regulatory protein (StAR), which facilitates the initial entry of cytosolic cholesterol into the mitochondrion, side-chain-cleavage enzyme (P450scc), 3β-hydroxy-steroid-dehydrogenase-2 (HSD3B2), 17-hydroxylase/17–20-lyase (P450c17) and aromatase which catalyzes the final step, are necessary for the conversion of cholesterol to estrogen. Expression and biologic activity StAR and aromatase were previously demonstrated in endometriosis but not in normal endometrium. PGE2 induces aromatase expression via the transcriptional factor steroidogenic factor-1 (SF1) in endometriosis, which is opposed by chicken-ovalbumin upstream-transcription factor (COUP-TF) and Wilms’ tumor-1 (WT1) in endometrium. To demonstrate a complete steroidogenic pathway leading to estrogen biosynthesis in endometriotic cells and the transcriptional mechanisms that regulate basal and PGE2-stimulated estrogen production in endometriotic cells and endometrium. Compared with normal endometrial tissues, expression of StAR, P450scc, HSD3B2 P450c17, aromatase and SF1 were significantly higher in endometriotic tissues. PGE2 induced the expression of all steroidogenic genes, production of progesterone, estrone and estradiol, and StAR promoter activity in endometriotic cells. Overexpression of SF1 induced, whereas COUP-TFII or WT1 suppressed, StAR promoter activity. PGE2 induced coordinate binding of SF1 to StAR and aromatase promoters, but decreased COUP-TFII binding in endometriotic cells. COUP-TFII or WT1 binding to both promoters was significantly higher in endometrial compared with endometriotic cells. Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.

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Available abstract

Products of at least five specific steroidogenic genes, including steroidogenic acute regulatory protein (StAR), which facilitates the initial entry of cytosolic cholesterol into the mitochondrion, side-chain-cleavage enzyme (P450scc), 3β-hydroxy-steroid-dehydrogenase-2 (HSD3B2), 17-hydroxylase/17–20-lyase (P450c17) and aromatase which catalyzes the final step, are necessary for the conversion of cholesterol to estrogen. Expression and biologic activity StAR and aromatase were previously demonstrated in endometriosis but not in normal endometrium. PGE2 induces aromatase expression via the transcriptional factor steroidogenic factor-1 (SF1) in endometriosis, which is opposed by chicken-ovalbumin upstream-transcription factor (COUP-TF) and Wilms’ tumor-1 (WT1) in endometrium. To demonstrate a complete steroidogenic pathway leading to estrogen biosynthesis in endometriotic cells and the transcriptional mechanisms that regulate basal and PGE2-stimulated estrogen production in endometriotic cells and endometrium. Compared with normal endometrial tissues, expression of StAR, P450scc, HSD3B2 P450c17, aromatase and SF1 were significantly higher in endometriotic tissues. PGE2 induced the expression of all steroidogenic genes, production of progesterone, estrone and estradiol, and StAR promoter activity in endometriotic cells. Overexpression of SF1 induced, whereas COUP-TFII or WT1 suppressed, StAR promoter activity. PGE2 induced coordinate binding of SF1 to StAR and aromatase promoters, but decreased COUP-TFII binding in endometriotic cells. COUP-TFII or WT1 binding to both promoters was significantly higher in endometrial compared with endometriotic cells. Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.

Key concepts: Steroidogenic factor 1, Cholesterol side-chain cleavage enzyme, Steroidogenic acute regulatory protein, Aromatase, Biology, Transcription factor, Estrogen, Internal medicine

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Prostaglandin E2 via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis — Research Paper | ScholarLens