Regulation of Steroid Hormone Action in Target Cells by Specific Hormone-Inactivating Enzymes

Roy, Arun K.

doi:10.3181/00379727-199-43356a

Cited by 67 publications

(21 citation statements)

References 26 publications

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“…Metal ions and hydroxyl radicals are thought to be responsible for oxidative damage to macromolecules such as DNA or lipids (44,45). Conjugation of estrogens makes them water soluble to be readily excreted or much more lipophilic to confer longer half-lives than the parent estrogens (46)(47)(48). It has been reported that these metabolic conjugation reactions play a critical role in deactivation of the redox active estrogen metabolites and marked reduction of the classical estrogenic activities of the parent estrogens (49,50).…”

Section: Metabolism Of Estrogenmentioning

confidence: 99%

Dual roles of estrogen metabolism in mammary carcinogenesis

Chang

2011

BMB Reports

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A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review. [BMB reports 2011; 44(7): 423-434]

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Section: Metabolism Of Estrogenmentioning

confidence: 99%

Dual roles of estrogen metabolism in mammary carcinogenesis

Chang

2011

BMB Reports

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“…UGT2B15 is expressed in luminal cells of the prostate, where DHT is formed, whereas, UGT2B17 is expressed in basal cells of the prostate, where dehydroepiandrosterone is converted into ADT and 3α-Diol [14]. In addition to facilitating the excretion, glucuronidation of androgens mediated by UGT2B15 and UGT2B17 in the prostate results in irreversible steric hindrance of androgens and abolishes the affinity of androgens to AR [15,16]. UGT2B15 and B17 are critical enzymes for the local inactivation of androgens.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor mediates the expression of UDP‐glucuronosyltransferase 2 B15 and B17 genes

et al. 2008

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BACKGROUND-Enhanced androgen receptor (AR) activity by increased testosterone availability may play important roles in prostate cancer progressing to castration resistant state. Comparison of expression profiles in androgen dependent and independent prostate tumors demonstrated a marked increase of the expression of UDP-glucuronosyltransferase 2B15 (UGT2B15), an androgen catabolic enzyme. We investigated mechanisms controlling the differential expression of UGT2B15 and B17 in response to androgen treatments.

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“…They grow independent of progesterone which is known as an important regulatory factor of oxidative 17 -HSD activity in vivo (Tseng & Gurpide 1974, 1975, 1979. Progesterone stimulates the expression of 17 -HSD1 (Poutanen et al 1990, 1992, Mäentausta et al 1993, of 17 -HSD2 (Casey et al 1994) as well as that of 17 -HSD4 (Kaufmann et al 1995). With these characteristics of the cell lines in mind, they represent an appropriate model to study the regulation of 17 -HSD isozymes independent of progesterone.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, oxidative 17 -hydroxysteroid dehydrogenase (17 -HSD) enzyme activity can control the occupancy of the estrogen receptor (Gurpide & Marks 1981; for review see Roy 1992, Penning 1997, Peltoketo et al 1999a. This is a prerequisite for the adequate differentiation of the endometrium in the secretory phase of the menstrual cycle.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines

Husen¹,

Psonka²,

Jacob-Meisel³

et al. 2000

Journal of Molecular Endocrinology

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In the endometrium two enzymes are known to convert estradiol to its inactive metabolite estrone: microsomal 17 -hydroxysteroid dehydrogenase type 2 (17 -HSD2) and peroxisomal 17 -HSD4. In order to elucidate the particular function of each of these two different enzymes, the human endometrial epithelial cell lines HEC-1-A and RL95-2 were examined with respect to the expression of 17 -HSD isozymes. They were compared with human endometrium in vivo. Non-radioactive in situ hybridization revealed both enzymes in glandular epithelial cells of human endometrium. The two cell lines were screened for mRNA expression of 17 -HSD 1-4 by RT-PCR and Northern blot. 17 -HSD2 and 4 could be detected by either method, 17 -HSD1 only by RT-PCR, 17 -HSD3 not at all. Both cell lines were proven to have no receptor for progesterone which is known as a physiological inducer of several 17 -HSD isozymes. To study the regulation of 17 -HSD2 and 17 -HSD4, the concentration of fetal calf serum in the cell culture media was reduced stepwise to 0·3% by dilution with a defined serum replacement. This treatment led to an inhibition of 17 -HSD2 mRNA expression and an increase in the mRNA expression of 17 -HSD4. Concomitantly, distinct morphological changes were observed, such as a decrease in the number and length of microvilli and a decrease in the formation of domes on top of the monolayers.The endometrial epithelial cell lines HEC-1-A and RL95-2 represent a suitable in vitro model for further studies of the differential expression of the major endometrial HSD isozymes, independent of the effect of progesterone.

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Regulation of Steroid Hormone Action in Target Cells by Specific Hormone-Inactivating Enzymes

Cited by 67 publications

References 26 publications

Dual roles of estrogen metabolism in mammary carcinogenesis

Dual roles of estrogen metabolism in mammary carcinogenesis

Androgen receptor mediates the expression of UDP‐glucuronosyltransferase 2 B15 and B17 genes

Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines

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