Provencher P H, Roy R, Bélanger A
CHUL Research Center, Sainte-Foy, Quebec, Canada.
Endocrinology. 1992 May;130(5):2717-24. doi: 10.1210/endo.130.5.1315255.
The presence of fatty acid ester derivatives of pregnenolone (PFA) has been recently reported in guinea pig plasma and adrenals. Moreover, it has equally been demonstrated that PFA is present in plasma lipoproteins, including high density lipoproteins (HDL) and low density lipoproteins (LDL). We report here the conversion of LDL- and HDL-incorporated [3H]PFA in guinea pig and bovine adrenocortical cells into nonconjugated steroids, thus indicating that PFA can be used as substrate for steroid production. When guinea pig glomerulosa-fasciculata (FG) cells were incubated for 48 h in the presence of either LDL-incorporated [3H]PFA or HDL-incorporated [3H]PFA, 66 +/- 2% and 47 +/- 1% of the added radioactivity were converted to nonconjugated steroids, respectively. The transformation of LDL-incorporated [3H]PFA into nonconjugated steroids was further increased in FG cells when 10 nmol/liter ACTH were present in the culture medium. This ACTH-induced liberation of nonconjugated steroids from LDL-incorporated [3H]PFA was strongly inhibited by a 10-fold excess of unlabeled LDL, while no competitive effect of unlabeled HDL was observed on the generation of tritiated nonconjugated steroids from HDL-incorporated [3H]PFA. Moreover, nonconjugated metabolites formed during incubation of FG cells with LDL-incorporated [3H]PFA and HDL-incorporated [3H]PFA resembled those observed when FG cells were incubated with tritiated pregnenolone. The formation of nonconjugated steroids was similarly observed when lipoprotein-incorporated [3H]PFA was incubated with bovine adrenocortical cells. Our data suggest that [3H]PFA incorporated into lipoproteins can be internalized into adrenal cells, after which the [3H]PFA is hydrolyzed into nonconjugated pregnenolone, which is readily used as substrate for adrenal steroidogenesis.
最近有报道称，豚鼠血浆和肾上腺中存在孕烯醇酮的脂肪酸酯衍生物（PFA）。此外，同样已证明PFA存在于血浆脂蛋白中，包括高密度脂蛋白（HDL）和低密度脂蛋白（LDL）。我们在此报告，豚鼠和牛肾上腺皮质细胞中，与LDL和HDL结合的[3H]PFA可转化为非共轭类固醇，这表明PFA可作为类固醇生成的底物。当豚鼠球状带-束状带（FG）细胞在含有与LDL结合的[3H]PFA或与HDL结合的[3H]PFA的情况下孵育48小时时，分别有66±2%和47±1%的添加放射性转化为非共轭类固醇。当培养基中存在10 nmol/升促肾上腺皮质激素（ACTH）时，FG细胞中与LDL结合的[3H]PFA向非共轭类固醇的转化进一步增加。这种由ACTH诱导的从与LDL结合的[3H]PFA中释放非共轭类固醇的过程，被10倍过量的未标记LDL强烈抑制，而未观察到未标记HDL对从与HDL结合的[3H]PFA中生成氚化非共轭类固醇有竞争作用。此外，FG细胞与与LDL结合的[3H]PFA和与HDL结合的[3H]PFA孵育期间形成的非共轭代谢物，类似于FG细胞与氚化孕烯醇酮孵育时观察到的代谢物。当与脂蛋白结合的[3H]PFA与牛肾上腺皮质细胞一起孵育时，同样观察到了非共轭类固醇的形成。我们的数据表明，与脂蛋白结合的[3H]PFA可被肾上腺细胞内化，之后[3H]PFA被水解为非共轭孕烯醇酮，后者很容易用作肾上腺类固醇生成的底物。
