Estrogen stimulation of P450 cholesterol side-chain cleavage activity in cultures of human placental syncytiotrophoblasts
Estrogen stimulation of P450 cholesterol side-chain cleavage activity in cultures of human placental syncytiotrophoblasts
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DOI：
10.1095/biolreprod56.1.272
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发表时间：
1997-01-01
影响因子：
3.6
通讯作者：
Albrecht, ED
中科院分区：
文献类型：
--
作者：
Babischkin, JS;Grimes, RW;Albrecht, ED
本研究确定了雌激素是否在调节P450胆固醇侧链切割酶（P450(scc)）和/或新生/去酯化胆固醇途径中发挥作用，这些途径参与了人合胞滋养细胞内孕酮的生物合成。用雌二醇培养人胎盘合胞滋养细胞48小时，用25-羟基胆固醇生成孕酮的方法测定P450（scc）活性。雌二醇浓度为10（-7）或10(-6)M和25-羟基胆固醇使合胞滋养细胞（ng/0.5 × 10(6)个细胞）产生的平均（+/- SE）黄体酮增加到19.2 +/- 1.1，比未处理的对照组（9.4 +/- 0.8）高104% (p < 0.001)，比单独使用25-羟基胆固醇（12.6 +/- 0.9）高52% （p < 0.001）。孕酮分泌的刺激显然不是孕酮对其主要代谢物代谢变化的结果，因为在这些条件下，20 α -羟基孕酮-4-烯-3- 1代表了一个次要的分泌成分（0.7-1.7 ng/0.5 x 10(6)个细胞），并且雌激素的水平没有实质性改变。与雌二醇对P450（scc）活性的刺激作用相反，雌激素既没有改变P450(scc) mRNA水平，也没有改变3-羟基-3-甲基戊二酰辅酶- a还原酶和胆固醇酯水解酶-限速酶的活性，分别用于培养的合胞滋养细胞中胆固醇形成的新生和脱酯化途径。综上所述，这些结果表明雌激素调节孕酮生物合成途径的P450（scc）组分，我们认为这表明灵长类动物怀孕期间合胞滋养细胞的功能/生化分化。
The present study determined whether estrogen has a role in regulating the P450 cholesterol side-chain cleavage enzyme (P450(scc)) and/or de novo/deesterification cholesterol pathways involved in progesterone biosynthesis within human syncytiotrophoblasts. Human placental syncytiotrophoblasts were cultured for 48 h with estradiol, and P450(scc) activity was determined by the formation of progesterone from 25-hydroxycholesterol. Estradiol at 10(-7) or 10(-6) M and 25-hydroxycholesterol increased mean (+/- SE) progesterone production by syncytiotrophoblasts (ng/0.5 x 10(6) cells) to a value (19.2 +/- 1.1) that was 104% (p < 0.001) higher than that of the untreated controls (9.4 +/- 0.8) and 52% higher (p < 0.001) than with 25-hydroxycholesterol alone (12.6 +/- 0.9). The stimulation of progesterone secretion apparently was not the result of a change in progesterone metabolism to its principal metabolite, because 20 alpha-hydroxypregn-4-en-3-one represented a minor secretory component (0.7-1.7 ng/0.5 x 10(6) cells) under these conditions, and levels were not substantially altered by estrogen. In contrast to the stimulatory effect of estradiol on P450(scc) activity, estrogen did not alter either the P450(scc) mRNA levels or the activities of 3-hydroxy-3-methylglutaryl coenzyme-A reductase and cholesterol ester hydrolase-rate-limiting enzymes for the de novo and deesterification pathways, respectively, for cholesterol formation in syncytiotrophoblasts in culture. Collectively, these results indicate that estrogen regulates the P450(scc) component of the progesterone biosynthetic pathway, which we suggest signals functional/biochemical differentiation of syncytiotrophoblasts during primate pregnancy.