Osawa Y, Ohnishi S, Yarborough C, Ohigashi S, Kosaki T, Hashino M, Yanaihara T, Nakayama T
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
Steroids. 1990 Apr;55(4):165-9. doi: 10.1016/0039-128x(90)90105-k.
19-Hydroxyandrostenedione (19-OHA) is secreted from the adrenal glands in men and women and also from the placenta during pregnancy. It has been found to cause hypertension in animal models. We have synthesized [7,7-2H2]-19-OHA with high deuterium content and, together with [7,7-2H2]A and [9,11-2H2]estrone (E1), have developed a quantitative assay of serum level 19-OHA, A, and E1 using the gas chromatography/mass spectrometry-mass fragmentography method to monitor individual subjects throughout pregnancy. The labeled 19-OHA, used as internal standard, showed only 6.73% of unlabeled compound. Recovery of standard 19-OHA, A, and E1 (5,000 pg each) added to male plasma was 97.4 +/- 2.3%, 96.3 +/- 2.1%, and 100.1 +/- 4.1% (mean +/- SD), respectively; the intraassay coefficient of variation was 2.1%, 3.5%, and 3.8%, respectively. Ten pregnant subjects without complications and 10 pregnant subjects near term with hypertension were selected (with informed consent). The 19-OHA and E1 serum concentrations of maternal venous blood from uncomplicated pregnancies increased significantly as gestation progressed (19-OHA: first trimester, 225 +/- 72; second trimester, 656 +/- 325; third trimester, 1,518 +/- 544 pg/ml), reaching the highest level at delivery (19-OHA: 1,735 +/- 684 pg/ml). Whereas a positive correlation was found between the level of 19-OHA and E1, no apparent change of the A level was observed during pregnancy. Levels of the three steroid hormones in pregnancy complicated by hypertension in the second and third trimester were not found to be significantly different from those of normal pregnancy (19-OHA of hypertensive subjects: second trimester, 762 +/- 349; third trimester, 1,473 +/- 491 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
19-羟基雄烯二酮(19-OHA)在男性和女性体内由肾上腺分泌,孕期还可由胎盘分泌。已发现在动物模型中它可导致高血压。我们合成了高氘含量的[7,7-2H₂]-19-OHA,并与[7,7-2H₂]雄烯二酮(A)和[9,11-2H₂]雌酮(E1)一起,采用气相色谱/质谱-质量碎片分析法建立了血清中19-OHA、A和E1水平的定量检测方法,以监测整个孕期的个体。用作内标的标记19-OHA仅为未标记化合物的6.73%。添加到男性血浆中的标准19-OHA、A和E1(各5000 pg)的回收率分别为97.4±2.3%、96.3±2.1%和100.1±4.1%(均值±标准差);批内变异系数分别为2.1%、3.5%和3.8%。选取了10名无并发症的孕妇和10名足月高血压孕妇(均已签署知情同意书)。无并发症妊娠孕妇母体静脉血中19-OHA和E1的血清浓度随孕周增加而显著升高(19-OHA:孕早期,225±72;孕中期,656±325;孕晚期,1518±544 pg/ml),在分娩时达到最高水平(19-OHA:1735±684 pg/ml)。虽然19-OHA和E1水平之间呈正相关,但孕期A水平未观察到明显变化。未发现妊娠中晚期并发高血压的孕妇这三种甾体激素水平与正常妊娠有显著差异(高血压孕妇的19-OHA:孕中期,762±349;孕晚期,1473±491 pg/ml)。(摘要截取自250词)