Baggia S, Albrecht E D, Pepe G J
Department of Physiology, Eastern Virginia Medical School, Norfolk 23501.
Endocrinology. 1990 May;126(5):2742-8. doi: 10.1210/endo-126-5-2742.
We have previously shown that the change in transuteroplacental cortisol (F)-cortisone (E) metabolism in vivo from preferential reduction (E to F) at midgestation to oxidation by term (F to E) does not occur in baboons in which the production or action of estrogen have been blocked. Moreover, because the administration of androstenedione (delta 4A) to baboons increased estradiol (E2) production at midgestation and induced a pattern of F-E metabolism similar to that at term, we suggested that estrogen regulates placental F-E interconversion. The present study was designed to ascertain whether estrogen regulates the activity of the placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) enzyme catalyzing the oxidation of F to E. Placentas were obtained on day 100 (n = 10) and day 165 (n = 10) of gestation (term = day 184) from untreated baboons, on day 100 from animals (n = 7) treated with delta 4A between days 70-100 of gestation, and on day 165 from animals in which placental estrogen was decreased by fetectomy (n = 5) on day 100 of gestation. Tissue was homogenized in phosphate buffer (pH 7.4) and microsomal fractions (105,000 x g) incubated (37 C; 2 min) in buffer containing 2.7 mM NAD+ and 0.03-1.0 microM [3H]F. Serum concentrations of E2 (nanograms per ml) in untreated baboons on day 100 (0.7 +/- 0.2) were 3-fold lower than those at term, increased (P less than 0.05) by delta 4A treatment (2.4 +/- 0.3), and decreased (0.12 +/- 0.01; P less than 0.05) by fetectomy. The specific activity (picomoles of E per min/mg protein) of placental 11 beta HSD in untreated baboons at midgestation (134 +/- 17) was increased (P less than 0.01) 3-fold by delta 4A treatment. Enzyme activity at term (148 +/- 29) was similar to that at midgestation, but markedly decreased (P less than 0.01) by fetectomy (16 +/- 4). Placental capacity to oxidize F to E (micromoles per min/placenta) in untreated baboons was 3-fold greater (P less than 0.01) at term (88 +/- 15) than at midgestation and was markedly reduced (P less than 0.01) by fetectomy (3 +/- 1). Collectively, these findings indicate that the activity of the placental 11 beta HSD enzyme catalyzing the oxidation of F to E is increased in baboons in which placental estrogen production was elevated at midgestation and decreased in animals when estrogen formation was inhibited by fetectomy.(ABSTRACT TRUNCATED AT 400 WORDS)
我们之前已经表明，在体内，经胎盘的皮质醇（F）-可的松（E）代谢变化，即从妊娠中期的优先还原（E转化为F）到足月时的氧化（F转化为E），在雌激素产生或作用被阻断的狒狒中不会发生。此外，由于给狒狒注射雄烯二酮（δ4A）会增加妊娠中期的雌二醇（E2）产生，并诱导出一种与足月时相似的F-E代谢模式，我们认为雌激素调节胎盘F-E的相互转化。本研究旨在确定雌激素是否调节催化F氧化为E的胎盘11β-羟基类固醇脱氢酶（11βHSD）的活性。在妊娠第100天（n = 10）和第165天（n = 10）（足月为第184天）从未经处理的狒狒获取胎盘，在妊娠第100天从妊娠70 - 100天期间接受δ4A处理的动物（n = 7）获取胎盘，以及在妊娠第165天从妊娠第100天进行胎儿切除术（n = 5）从而使胎盘雌激素减少的动物获取胎盘。将组织在磷酸盐缓冲液（pH 7.4）中匀浆，微粒体部分（105,000×g）在含有2.7 mM NAD +和0.03 - 1.0 μM [3H]F的缓冲液中于37℃孵育2分钟。未经处理的狒狒在第100天的血清E2浓度（每毫升纳克数）（0.7±0.2）比足月时低3倍，经δ4A处理后升高（P < 0.05）（2.4±0.3），而经胎儿切除术降低（0.12±0.01；P < 0.05）。未经处理的狒狒在妊娠中期胎盘11βHSD的比活性（每分钟每毫克蛋白质产生的E的皮摩尔数）（134±17）经δ4A处理后增加（P < 0.01）3倍。足月时的酶活性（148±29）与妊娠中期相似，但经胎儿切除术显著降低（P < 0.01）（16±4）。未经处理的狒狒中胎盘将F氧化为E的能力（每分钟每胎盘微摩尔数）在足月时（88±15）比妊娠中期大3倍（P < 0.01），经胎儿切除术则显著降低（P < 0.01）（3±1）。总体而言，这些发现表明，在妊娠中期胎盘雌激素产生增加的狒狒中，催化F氧化为E的胎盘11βHSD酶的活性增加，而在雌激素形成因胎儿切除术受到抑制的动物中该活性降低。（摘要截断于400字）
