Hormonal regulation of cytochrome P450 enzymes, cholesterol side-chain cleavage and 17 alpha-hydroxylase/C17-20 lyase in Leydig cells.
Hormonal regulation of cytochrome P450 enzymes, cholesterol side-chain cleavage and 17 alpha-hydroxylase/C17-20 lyase in Leydig cells.
复制标题
Leydig 细胞中细胞色素 P450 酶、胆固醇侧链裂解和 17 α-羟化酶/C17-20 裂解酶的激素调节。
DOI：
10.1095/biolreprod42.3.399
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发表时间：
1990
影响因子：
3.6
通讯作者：
Payne,AH
中科院分区：
文献类型：
--
作者：
Payne,AH
睾丸间质细胞中的睾酮生物合成依赖于两种细胞色素P450酶，胆固醇侧链切割（P45 O 5）和17 α-羟化酶/C17-20 lya。se（P4501 7&.这些伊沃酶的表达受LII通过其第二信使环腺苷3 '，5'-单磷酸（cAMP）和特定类固醇激素作用的差异调节。P4505在正常小鼠Leydig细胞和MA-JO肿瘤Levdig细胞中组成型表达。慢性cAMP刺激增加450 SCC mRNA和从头P45 O 5蛋白合成的稳态水平。与此相反，cAMP是强制性的从头合成P450 J7 cx在正常小鼠Leydig细胞; P45 OI 7a合成停止在黄体生成素或cAMP的情况下。MA-JO肿瘤Leydig细胞不表达P45017 a，即使在用cAMP处理后。P4501 7a在Leydig细胞中的量由睾酮通过两种不同的机制负调节。在低浓度下，睾酮通过雄激素受体抑制cAMP诱导的P4501 7a'的合成，而在高浓度下，这种类固醇通过氧介导的机制增加酶的降解速率。组成性和cAMP诱导的P45 O 5蛋白合成和mRNA的稳态水平都受到糖皮质激素的调节。在正常小鼠Leydig细胞中，糖皮质激素抑制P45 O 5的合成和pso 5 mRNA的稳态水平，而糖皮质激素刺激肿瘤Leydig细胞中P45 O 5的合成和nRNA的水平。因此，这两种细胞色素P450酶在Leydig细胞中的调节是复杂的：不仅不同的因子调节同一细胞内的每种酶，而且与肿瘤Leydig细胞相比，正常Leydig细胞中的相同酶受到不同机制的调节。许多问题仍然存在，包括调节机制，确定物种和组织特异性表达的P45 OSC和450 J7 a，以及cAMP非依赖性表达的P4505最近可用的新的分子工具，应有助于更好地了解的复杂性，P450的类固醇合成细胞的表达调节。
Testosterone biosynthesis in Leydig cells is dependent on two cvtochrome P450 enzymes, cholesterol sidechain cleavage (P45O5) and 1 7a-hydroxylase/C17-20 lya. se (P4501 7&. The expression of these Iwo enzymes is differentially regulated by LII acting via its second messenger, cyclic adenosine 3’, 5’-monophosphate(cAMP), and by specific steroid hormones. P4505 is constitutively expressed in normal mouse Leydig cells and in MA-JO tumor Levdig cells. Chronic cAMP stimulation increases the steady state levels of 450scc mRNA and de novo P45O5 protein synthesis. In contrast, cAMP is obligatory for de novo synthesis of P450 J7cx in normal mouse Leydig cells; P45OI7a synthesis ceases in the absence of luteinizing hormone or cAMP. MA-JO tumor Leydig cells do not express P45017a even after treatment with cAMP. The amount of P4501 7a in Leydig cells is negatively regulated by testosterone acting by two distinct mechanisms. At low concentrations, testosterone acts via the androgen receptor to repress cAMP-induced synthesis of P4501 7a’whereas at high concentrations this steroid increases the rate of degradation of the enzyme by an oxygen-mediated mechanism. Both constitutive and cAMP-induced synthesis of P45O5 protein and steady state levels of mRNA are modulated by glucocorticoids. in normal mouse Leydig cells, glucocorticoids repress P45O5 synthesis and steady state levels of pso5 mRNA, whereas glucocorticoids stimulate P45O5 synthesis and levels of, nRNA in the tumor Leydig cells. Thus regulation of these two cytochrome P450 enzymes in Leydig cells is complex: not only do different factors regulate each enzyme within the same cell, but the same enzyme is regulated by different mechanisms in normal compared to tumor Leydig cells. Many questions remain, including the regulatory mechanisms that determine species and tissue specific expression of P45OSC and 450J7a as well as cAMP-independent expression of P4505 The recent availability of new molecular tools should contribute to a better understanding of the complexity of the regulation of P450 expression in steroidogenic cells.