Albrecht E D, Pepe G J
Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore 21201.
Endocr Rev. 1990 Feb;11(1):124-50. doi: 10.1210/edrv-11-1-124.
Substantial advances in our understanding of placental function have resulted from recent establishment of in vitro approaches, such as cell culture, and application of molecular methods to study placental steroidogenesis. Insight into the processes of placental cell differentiation and hormonal function has been gained from culture of relatively pure preparations of cytotrophoblast. Various factors, e.g. cAMP and peptide growth factors, have been shown to have striking effects on progesterone and estrogen formation by placental tissue under in vitro conditions. Using advanced molecular approaches, the genes governing specific enzymes critical to placental steroidogenesis have been identified. Regulation of the mRNAs encoding specific enzyme peptides and thus expression of the genes by factors, such as cAMP, have been elucidated by Northern analysis and other techniques. It is critical that these contemporary approaches continue to be implemented aggressively to further elucidate placental function. However, it is clear from a survey of the literature, particularly of the past decade, that the vast majority of investigation in the area has been conducted in vitro. It is essential to determine whether the factors that have been observed to regulate placental endocrine function in vitro are operable in vivo. It is only with in vivo study that the dynamics of steroidogenesis and the complex functional relationships between placenta, fetus, and mother will be uncovered and understood. It is increasingly evident that the regulation of placental steroidogenesis involves autocrine and/or paracrine mechanisms, similar to those integral to hormone biosynthesis within other reproductive organs, e.g. ovary and testis. For example, as discussed above, estrogen regulates LDL uptake and P-450scc, and thus apparently is involved in generating substrate for progesterone production within the placenta. Conversely, progesterone has effects on 17 beta-hydroxysteroid oxidoreductase and thus the metabolism of estradiol, while androgens exert marked inhibitory effects on placental progesterone formation, at least in vitro. Not surprisingly, the regulation of placental progesterone and estrogen formation also is multifactorial. Thus, aromatase activity is stimulated synergistically by cAMP and phorbol esters, an effect that is suppressed by peptide growth factors. Therefore, the autocrine/paracrine and multifactorial regulation of hormone biosynthesis that has been relatively well documented in other tissues should be recognized as important in the primate placenta. Finally, the basic mechanisms underlying regulation of steroidogenesis within the fetoplacental unit during primate pregnancy appear similar, in important ways, to those of widely used laboratory animals, such as the rat and rabbit.(ABSTRACT TRUNCATED AT 400 WORDS)
对胎盘功能认识的重大进展源于近期体外研究方法的建立，如细胞培养，以及分子方法在胎盘类固醇生成研究中的应用。通过培养相对纯净的细胞滋养层制剂，人们对胎盘细胞分化和激素功能的过程有了深入了解。在体外条件下，已证明多种因素，如环磷酸腺苷（cAMP）和肽生长因子，对胎盘组织产生孕酮和雌激素有显著影响。利用先进的分子方法，已确定了对胎盘类固醇生成至关重要的特定酶的调控基因。通过Northern分析和其他技术，已阐明了诸如cAMP等因素对编码特定酶肽的mRNA的调控以及基因的表达。至关重要的是，必须继续积极采用这些现代方法，以进一步阐明胎盘功能。然而，从文献调查，尤其是过去十年的文献来看，该领域的绝大多数研究都是在体外进行的。确定在体外观察到的调节胎盘内分泌功能的因素在体内是否起作用至关重要。只有通过体内研究，才能揭示和理解类固醇生成的动态过程以及胎盘、胎儿和母亲之间复杂的功能关系。越来越明显的是，胎盘类固醇生成的调节涉及自分泌和/或旁分泌机制，这与其他生殖器官（如卵巢和睾丸）内激素生物合成所必需的机制类似。例如，如上文所述，雌激素调节低密度脂蛋白摄取和细胞色素P450侧链裂解酶（P-450scc），因此显然参与了胎盘中孕酮生成底物的产生。相反，孕酮对17β-羟类固醇氧化还原酶有影响，从而影响雌二醇的代谢，而雄激素至少在体外对胎盘孕酮生成有显著抑制作用。毫不奇怪，胎盘孕酮和雌激素生成的调节也是多因素的。因此，cAMP和佛波酯协同刺激芳香化酶活性，而肽生长因子则抑制这种作用。因此，在其他组织中已有较多记录的激素生物合成的自分泌/旁分泌和多因素调节在灵长类胎盘里也应被视为重要的。最后，灵长类动物孕期胎儿-胎盘单位内类固醇生成调节的基本机制在重要方面似乎与广泛使用的实验动物（如大鼠和兔子）相似。（摘要截选至400字）
