Rane A, Henningsson S, Ask B, Ladona M G
Department of Clinical Pharmacology, Akademiska Hospital, Uppsala, Sweden.
J Steroid Biochem Mol Biol. 1992 Oct;43(4):335-41. doi: 10.1016/0960-0760(92)90168-i.
The immunoidentified human fetal liver and adrenal microsomal contents of cytochromes P450IIIA and P450XVIIA1 were compared to the metabolism of steroids and ethylmorphine. In fetal liver microsomes, 16 alpha-hydroxylation of dehydroepiandrosterone (DHA) was catalyzed at a high rate in almost all investigated specimens and accompanied by a high ethylmorphine N-demethylase activity. Progesterone 16 alpha- and 17 alpha-hydroxylation was found only in the livers with the highest DHA 16 alpha-hydroxylation activities, while 21-hydroxylation of progesterone was catalyzed only occasionally in these samples. In fetal adrenal microsomes, 21-hydroxylation of progesterone to 11-desoxycorticosterone (DOC) and 11-desoxycortisol (DOCOL) was catalyzed. In contrast to fetal liver, the adrenals also catalyzed the 17 alpha-hydroxylation of pregnenolone and the formation of DHA from 17 alpha-OH-pregnenolone. 16 alpha-hydroxylation of DHA and ethylmorphine N-demethylation were modest in the adrenals. P450IIIA/HLp was immunoidentified in all investigated liver specimens except two (18/20) in which no ethylmorphine N-demethylation or 16 alpha-hydroxylation of DHA was found. P450XVIIA1 bands were observed in 8/20 blots of liver specimens, but there was no correlation between the density of these bands and the 17 alpha-hydroxylation of progesterone. All 11 fetal adrenal samples catalyzed DHA 16 alpha-hydroxylation, although only 8 were positive for P450IIIA/HLp. All investigated adrenals were positive in regard of the P450XVIIA1 band, except one (8/9) with a low 17 alpha-hydroxylation of progesterone. All adrenal specimens catalyzed 21-hydroxylation of progesterone and contained P450C21 bands in immunoblots and all samples catalyzed the formation of DOC and DOCOL from progesterone. Our findings in the fetal livers show a correlation between the DHA 16 alpha-hydroxylation and immunoidentified P450IIIA/HLp bands. In adrenals, there was a correlation between the immunoidentified P450XVIIA1 bands and the 17 alpha-hydroxylation of progesterone.
对经免疫鉴定的人胎儿肝脏和肾上腺微粒体中细胞色素P450IIIA和P450XVIIA1的含量与类固醇及乙基吗啡的代谢情况进行了比较。在胎儿肝脏微粒体中，几乎所有被研究的标本中脱氢表雄酮（DHA）的16α-羟基化反应都以较高速率催化进行，同时伴有较高的乙基吗啡N-脱甲基酶活性。仅在DHA 16α-羟基化活性最高的肝脏中发现了孕酮的16α-和17α-羟基化反应，而这些样本中孕酮的21-羟基化反应只是偶尔被催化。在胎儿肾上腺微粒体中，催化了孕酮向11-脱氧皮质酮（DOC）和11-脱氧皮质醇（DOCOL）的21-羟基化反应。与胎儿肝脏不同，肾上腺还催化了孕烯醇酮的17α-羟基化反应以及由17α-羟基孕烯醇酮生成DHA的反应。肾上腺中DHA的16α-羟基化反应和乙基吗啡N-脱甲基反应程度适中。除了两个未发现乙基吗啡N-脱甲基反应或DHA的16α-羟基化反应的肝脏标本外（20个标本中有18个），在所有被研究的肝脏标本中都经免疫鉴定出了P450IIIA/HLp。在20个肝脏标本的印迹中有8个观察到了P450XVIIA1条带，但这些条带的密度与孕酮的17α-羟基化反应之间没有相关性。所有11个胎儿肾上腺样本都催化了DHA的16α-羟基化反应，尽管只有8个样本P450IIIA/HLp呈阳性。除了一个孕酮17α-羟基化反应较低的样本外（9个样本中有8个），所有被研究的肾上腺在P450XVIIA1条带方面均呈阳性。所有肾上腺标本都催化了孕酮的21-羟基化反应，免疫印迹中含有P450C21条带，并且所有样本都催化了由孕酮生成DOC和DOCOL的反应。我们在胎儿肝脏中的研究结果表明，DHA的16α-羟基化反应与经免疫鉴定的P450IIIA/HLp条带之间存在相关性。在肾上腺中，经免疫鉴定的P450XVIIA1条带与孕酮的17α-羟基化反应之间存在相关性。
