Localization of type 1 17beta-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi

Abstract

The 17 -hydroxysteroid dehydrogenases (17 -HSDs) play a key role in the synthesis of sex steroids. The hallmark of this family of enzymes is the interconversion, through their oxydoreductive reactivity at position C17, of 17-keto-and 17 -hydroxy-steroids. Because this reaction essentially transforms steroids having low binding activity for the steroid receptor to their more potent 17 -hydroxysteroids isoforms, it is crucial to the control of the physiological activities of both estrogens and androgens. The human placenta produces large amounts of progesterone and estrogens throughout pregnancy. The placental type 1 17 -HSD enzyme (E17 -HSD) catalyzes the reduction of the low activity estrogen, estrone, into the potent estrogen, estradiol. We studied the cell-specific expression of type 1 17 -HSD in human term placental villous tissue by combining in situ hybridization to localize type 1 17 -HSD mRNA with immunohistochemistry using an antibody against human placental lactogen, a trophoblast marker. Immunolocalization of E17 -HSD was also performed. To ascertain whether other steroidogenic enzymes are present in the same cell type, cytochrome P450 cholesterol side-chain cleavage (P450scc), P450 aromatase, and type 1 3 -hydroxysteroid dehydrogenase (3 -HSD) were also localized by immunostaining. Our results showed that the syncytium is the major steroidogenic unit of the fetal term villi. In fact, type 1 17 -HSD mRNA and protein, as well as P450scc, P450 aromatase, and 3 -HSD immunoreactivities were found in these cells. In addition, our results revealed undoubtedly that extravillous cytotrophoblasts (CTBs), e.g. those from which cell columns of anchoring villous originate, also express the type 1 17 -HSD gene. However, CTBs lying beneath the syncytial layer, e.g. those from which syncytiotrophoblasts develop, contained barely detectable amounts of type 1 17 -HSD mRNA as determined by in situ hybridization. These findings, along with those from other laboratories confirm the primordial role of the syncytium in the synthesis of steroids during pregnancy. In addition, our results indicate for the first time that CTBs differentiating along the invasive pathway contain type 1 17 -HSD mRNA.

Expression of P450 aromatase and 17β-hydroxysteroid dehydrogenase type 1 at fetal–maternal interface during tubal pregnancy

“…In the present study, P450arom and 17HSD1 were exclusively identified in the ST cells of FV during tubal pregnancy. The data are in agreement with earlier findings showing that P450arom and 17HSD1 are present in ST cells [11,17], which further supports the assumption that ST cells are the main cell type for placental steroid hormone biosynthesis. On the other hand, our results indicate that the occurrence of tubal pregnancy is unlikely to affect the production of estrogens in the placenta.…”

“…Also, it has been shown that CT cells freshly isolated from full-term placenta contain 17HSD1 [16]. In addition, 17HSD1 was immunolocalized in invasive CT cells of full-term placenta [17]. Our recent study demonstrated that cultured CT cells purified from first-trimester placenta express both P450arom and 17HSD1 and are capable of converting dehydroepiandrosterone and A-dione to E 2 [18].…”

Hydroxysteroid (17-β) Dehydrogenase 1 Is Dysregulated by Mir-210 and Mir-518c That Are Aberrantly Expressed in Preeclamptic Placentas

“…18 Thus, it is likely that HSD17B1 expression is dysregulated in an miRNA-mediated manner in the STB of preeclamptic placentas. It should be noted that Winn et al 19 also identified HSD17B1 previously as a pronouncedly downregulated gene in preeclamptic placentas by comprehensive analysis using microarray.…”

Human type 2 17beta-hydroxysteroid dehydrogenase in umbilical vein and artery endothelial cells: differential inactivation of sex steroids according to the vessel type

“…Such contamination is easily noticeable since endothelial and fibroblastic phenotypes are distinguishable visually. HUAEC and HUVEC were included in experiments at comparable cell passage number (5)(6)(7)(8)(9)(10).…”

“…In human placenta, 17bHSD1 is exclusively expressed by syncytium of floating villi [4,7,8], whereas 17bHSD2 is only expressed by endothelial cells of fetal vessels [8][9][10]. In term placenta and stem villi [11], some large vessels strongly express 17bHSD2 mRNA and protein, while others show a barely detectable signal [9,10].…”