Bonenfant M, Provost P R, Drolet R, Tremblay Y
Laboratory of Ontogeny and Reproduction, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Canada G1V 4G2.
J Endocrinol. 2000 May;165(2):217-22. doi: 10.1677/joe.0.1650217.
The 17beta-hydroxysteroid dehydrogenases (17beta-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 17beta-hydroxy-steroids. Because this reaction essentially transforms steroids having low binding activity for the steroid receptor to their more potent 17beta-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 17beta-HSD enzyme (E17beta-HSD) catalyzes the reduction of the low activity estrogen, estrone, into the potent estrogen, estradiol. We studied the cell-specific expression of type 1 17beta-HSD in human term placental villous tissue by combining in situ hybridization to localize type 1 17beta-HSD mRNA with immunohistochemistry using an antibody against human placental lactogen, a trophoblast marker. Immunolocalization of E17beta-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 3beta-hydroxysteroid dehydrogenase (3beta-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 17beta-HSD mRNA and protein, as well as P450scc, P450 aromatase, and 3beta-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 17beta-HSD gene. However, CTBs lying beneath the syncytial layer, e.g. those from which syncytiotrophoblasts develop, contained barely detectable amounts of type 1 17beta-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 17beta-HSD mRNA.
17β-羟基类固醇脱氢酶（17β-HSDs）在性类固醇的合成中起关键作用。这类酶的特点是通过其在C17位的氧化还原反应，实现17-酮类固醇和17β-羟基类固醇的相互转化。由于该反应基本上将对类固醇受体结合活性低的类固醇转化为其活性更强的17β-羟基类固醇异构体，因此对雌激素和雄激素生理活性的控制至关重要。人胎盘在整个孕期会产生大量的孕酮和雌激素。胎盘1型17β-HSD酶（E17β-HSD）催化低活性雌激素雌酮还原为活性较强的雌激素雌二醇。我们通过将原位杂交定位1型17β-HSD mRNA与使用抗人胎盘催乳素（一种滋养层标志物）抗体的免疫组织化学相结合，研究了1型17β-HSD在人足月胎盘绒毛组织中的细胞特异性表达。还进行了E17β-HSD的免疫定位。为确定同一细胞类型中是否存在其他类固醇生成酶，还通过免疫染色对细胞色素P450胆固醇侧链裂解酶（P450scc）、P450芳香化酶和1型3β-羟基类固醇脱氢酶（3β-HSD）进行了定位。我们的结果表明，合体滋养层是足月胎儿绒毛的主要类固醇生成单位。事实上，在这些细胞中发现了1型17β-HSD mRNA和蛋白，以及P450scc、P450芳香化酶和3β-HSD免疫反应性。此外，我们的结果无疑揭示，绒毛外细胞滋养层（CTBs），例如那些形成固定绒毛细胞柱的细胞，也表达1型17β-HSD基因。然而，通过原位杂交测定，位于合体滋养层下方的CTBs，例如那些形成合体滋养层的细胞，仅含有难以检测到的1型17β-HSD mRNA。这些发现以及其他实验室的研究结果证实了合体滋养层在孕期类固醇合成中的重要作用。此外，我们的结果首次表明，沿侵袭途径分化的CTBs含有1型17β-HSD mRNA。
