Hydroxysteroid Dehydrogenases 1 And 2 In Other Tissues

Beta Switch Program

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In addition to breast tissue, both 17HSD1 and 17HSD2 are expressed in another typical target tissue of female sex steroids, the endometrium. Using immunological methods, 17HSD1 has been localized in the surface and glandular epithelial cells when progesterone was present at concentrations characteristic of an ovulatory cy-cle.62 During the proliferative phase of the menstrual cycle, 17HSD1 staining was absent or minimal. However, it was maximal during the mid-secretory phase and disappeared rapidly thereafter. An antiprogestin given to women shortly after ovulation blocked the expression of 17HSD1 during the luteal phase of the cycle, suggesting progesterone receptor-mediated induction of the type 1 enzyme.63 Using in situ hybridization, the mRNA for 17HSD2 has also been localized in epithelial cells of the endometrium; but in contrast to 17HSD1, 17HSD2 expression was highest at the end of the cycle.38 Both 17HSD1 and 17HSD2 have been detected in human endometrium during the luteal phase of the cycle using Northern analysis, and 17HSD2 appears to be the predominant 17HSD,56 in accordance with the preferred oxidation of 17j6-hydroxysteroids in endometrial tissue.64 Differential expression of the two 17HSD enzymes with opposite activities in the same cell types may effectively modulate in-tracellular E2 concentrations during the menstrual cycle and thereby improve the control of E2 influence during menstrual variations.

There are few data on the expression of 17HSD1 and 17HSD2 in postmenopausal en-dometrium and endometrial carcinoma. Antibodies against 17HSD1 have revealed the enzyme in about 50% of carcinoma specimens.65 There was marked heterogeneity among 17HSD1-positive malignant tissue specimens; staining intensity varied greatly, showing both stained and unstained malignant epithelial cells.65 In endometrial cancer cell lines, very little type 1 activity has been detected, while some cell lines have shown high type 2 enzyme-like activity and expression of 17HSD2 mRNA.56 Of male sex steroid target tissues, 17HSD2 has been detected in normal and malignant prostate. Higher expression of 17HSD2 has been detected in benign prostatic hyperplasia compared with prostatic carcinoma.66 PC3, a prostate cancer cell line, also expresses 17HSD2.56

The type 2 enzyme is more widely distributed in tissues of humans and other animal species than 17HSD1. Strong expression has been detected in human liver, placenta, and small intestine and lower levels in the colon, kidney, and pancreas.56,67 Additional information on the physiological importance of the type 2 enzyme has been obtained by localizing it in mouse tissues: the enzyme is expressed in several epithelial layers of the gastrointestinal and urogenital tracts.36 The localization and intensity of 17HSD type 2 mRNA expression were, furthermore, identical in the gastrointestinal tracts of both male and female mice.36 During embryogenesis, its expression strongly increased in parallel with the fetal development of gastrointestinal organs.68 All of these data suggest a role for 17HSD2 in the inactivation of sex steroids and steroid-like compounds present in the intestinal contents. Both human and mouse 17HSD2 enzymes are also highly expressed in the placenta.38,68,69 Hence, 17HSD2 may maintain a barrier to the highly active 17^-hydroxy forms of sex steroids between mother and fetus.

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