Mason J I, Ushijima K, Doody K M, Nagai K, Naville D, Head J R, Milewich L, Rainey W E, Ralph M M
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9051.
J Steroid Biochem Mol Biol. 1993 Dec;47(1-6):151-9. doi: 10.1016/0960-0760(93)90069-9.
The appropriate expression of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD) is vital for mammalian reproduction, fetal growth and life maintenance. Several isoforms of 3 beta-HSD, the products of separate genes, have been identified in various species including man. Current investigations are targeted toward defining the processes that regulate the levels of specific isoforms in various steroidogenic tissues of man. High levels of expression of 3 beta-HSD were observed in placental tissues. It has been generally considered that the multinucleated syncytiotrophoblastic cells are the principal sites of 3 beta-HSD expression and, moreover, that 3 beta-HSD expression is intimately associated with cyclic AMP-promoted formation of syncytia. Herein we report the presence of 3 beta-HSD immunoreactive and mRNA species in uninucleate cytotrophoblasts in the chorion laeve, similar to that in syncytia but not cytotrophoblast placenta. In vitro, 3 beta-HSD levels in chorion laeve cytotrophoblasts were not increased with time nor after treatment with adenylate cyclase activators, whereas villous cytotrophoblasts spontaneously demonstrated progressive, increased 3 beta-HSD expression. Moreover, 3 beta-HSD synthesis appeared to precede morphologic syncytial formation. Thus high steroidogenic enzyme expression in placenta is not necessarily closely linked to formation of syncytia. Both Western immunoblot and enzymic activity analyses also indicated that the 3 beta-HSD expressed in these cytotrophoblastic populations was the 3 beta-HSD type I gene product (M(r), 45K) and not 3 beta-HSD type II (M(r), 44K) expressed in fetal testis. In cultures of fetal zone and definitive zone cell of human fetal adrenal, 3 beta-HSD expression was not detected until ACTH was added. ACTH, likely acting in a cyclic AMP-dependent process, induced 3 beta-HSD type II activity and mRNA expression. The higher level of 3 beta-HSD mRNA in definitive zone compared with fetal zone cells was associated with parallel increases in cortisol secretion relative to dehydroepiandrosterone sulfate formation.
3β-羟类固醇脱氢酶/δ5→4-异构酶（3β-HSD）的适度表达对于哺乳动物的繁殖、胎儿生长及维持生命至关重要。在包括人类在内的多种物种中，已鉴定出3β-HSD的几种同工型，它们是不同基因的产物。目前的研究旨在确定调节人类各种类固醇生成组织中特定同工型水平的过程。在胎盘组织中观察到3β-HSD的高表达水平。一般认为，多核合体滋养层细胞是3β-HSD表达的主要部位，此外，3β-HSD的表达与环磷酸腺苷促进的合体形成密切相关。在此我们报告，在平滑绒毛膜的单核细胞滋养层细胞中存在3β-HSD免疫反应性物质和mRNA，类似于合体细胞而非滋养层胎盘细胞中的情况。在体外，平滑绒毛膜滋养层细胞中的3β-HSD水平不会随时间增加，用腺苷酸环化酶激活剂处理后也不会增加，而绒毛滋养层细胞则自发地表现出3β-HSD表达的逐渐增加。此外，3β-HSD的合成似乎先于形态学上的合体形成。因此，胎盘中高类固醇生成酶表达不一定与合体形成密切相关。蛋白质免疫印迹和酶活性分析均表明，这些滋养层细胞群体中表达的3β-HSD是I型3β-HSD基因产物（分子量为45K），而非胎儿睾丸中表达的II型3β-HSD（分子量为44K）。在人胎儿肾上腺的胎儿带和永久带细胞培养物中，直到添加促肾上腺皮质激素（ACTH）后才检测到3β-HSD表达。ACTH可能通过依赖环磷酸腺苷的过程诱导II型3β-HSD活性和mRNA表达。与胎儿带细胞相比，永久带细胞中3β-HSD mRNA水平较高，这与皮质醇分泌相对于硫酸脱氢表雄酮形成的平行增加有关。
