Comparison of the Effects of Dibutyl and Monobutyl Phthalates on the Steroidogenesis of Rat Immature Leydig Cells.
Comparison of the Effects of Dibutyl and Monobutyl Phthalates on the Steroidogenesis of Rat Immature Leydig Cells.
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邻苯二甲酸二丁酯和邻苯二甲酸单丁酯对大鼠未成熟间质细胞类固醇生成的影响比较
DOI：
10.1155/2016/1376526
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发表时间：
2016
影响因子：
--
通讯作者：
Ge RS
中科院分区：
文献类型：
--
作者：
Li L;Chen X;Hu G;Wang S;Xu R;Zhu Q;Li X;Wang M;Lian QQ;Ge RS
邻苯二甲酸二丁酯（DBP）是一种广泛使用的合成邻苯二甲酸二酯，邻苯二甲酸单丁酯（MBP）是其主要代谢产物。DBP可释放到环境中，并可能干扰哺乳动物雄性生殖内分泌系统。然而，DBP和MBP抑制Leydig细胞类固醇生成的效力及其可能的机制尚不清楚。用0.05-50 μM DBP或MBP与睾酮合成调节剂或中间体联合培养大鼠未成熟Leydig细胞3 h。测定培养液中5α-雄甾烷酮和睾酮的浓度，qPCR检测雄激素生物合成基因的mRNA水平。测定DBP或MBP对CYP 11 A1、CYP 17 A1、SRD 5A 1和AKR 1C 14活性的直接作用。MBP在低至50 nM时抑制未成熟Leydig细胞的雄激素产生，而DBP需要50 μM才能抑制其雄激素产生。MBP在50 nM时主要下调Cyp 11 a1和Hsd 3b 1的表达水平。然而，50 μM DBP下调星星、Hsd 3b 1和Hsd 17 b3表达水平，并直接抑制CYP 11 A1和CYP 17 A1活性。总之，DBP被代谢为更有效的抑制剂MBP，其下调某些雄激素生物合成酶的表达水平。
Dibutyl phthalate (DBP) is a widely used synthetic phthalic diester and monobutyl phthalate (MBP) is its main metabolite. DBP can be released into the environment and potentially disrupting mammalian male reproductive endocrine system. However, the potencies of DBP and MBP to inhibit Leydig cell steroidogenesis and their possible mechanisms are not clear. Immature Leydig cells isolated from rats were cultured with 0.05–50 μM DBP or MBP for 3 h in combination with testosterone synthesis regulator or intermediate. The concentrations of 5α-androstanediol and testosterone in the media were measured, and the mRNA levels of the androgen biosynthetic genes were detected by qPCR. The direct actions of DBP or MBP on CYP11A1, CYP17A1, SRD5A1, and AKR1C14 activities were measured. MBP inhibited androgen production by the immature Leydig cell at as low as 50 nM, while 50 μM was required for DBP to suppress its androgen production. MBP mainly downregulated Cyp11a1 and Hsd3b1 expression levels at 50 nM. However, 50 μM DBP downregulated Star, Hsd3b1, and Hsd17b3 expression levels and directly inhibited CYP11A1 and CYP17A1 activities. In conclusion, DBP is metabolized to more potent inhibitor MBP that downregulated the expression levels of some androgen biosynthetic enzymes.