Benzo[a]pyrene reduces testosterone production in rat Leydig cells via a direct disturbance of testicular steroidogenic machinery.
Benzo[a]pyrene reduces testosterone production in rat Leydig cells via a direct disturbance of testicular steroidogenic machinery.
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苯并[a] pyrene通过直接干扰睾丸类固醇生成机制来降低大鼠leydig细胞中的睾丸激素的产生。
DOI：
10.1289/ehp.1003391
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发表时间：
2011-11
影响因子：
10.4
通讯作者：
Kim JM
中科院分区：
文献类型：
--
作者：
Chung JY;Kim YJ;Kim JY;Lee SG;Park JE;Kim WR;Yoon YD;Yoo KS;Yoo YH;Kim JM
背景：苯并[a]芘（B[a]P）是一种多环芳烃（PAH），是一种普遍存在的环境污染物，目前被怀疑是一种内分泌干扰物。睾丸是多环芳烃的重要靶点，但其对间质细胞类固醇生成的影响尚未引起足够的重视。目的：我们假设长期暴露于低浓度的 B[a]P 可能会通过改变类固醇生成蛋白来破坏 Leydig 细胞中睾酮的产生。结果：口服 B[a]P 会降低大鼠血清和睾丸液中睾酮水平。然而，尽管精原细胞凋亡显着增加，但我们没有观察到严重的睾丸萎缩或无精症。与对照细胞相比，体内用 B[a]P 引发的 Leydig 细胞在体外对人绒毛膜促性腺激素 (hCG) 或二丁基环磷酸腺苷的反应产生较少的睾酮。值得注意的是，睾酮水平的降低伴随着 Leydig 细胞中类固醇生成急性调节蛋白 (StAR) 和 3β-羟基类固醇脱氢酶 (3β-HSD) 表达的降低，以及细胞色素 P450 侧链裂解 (P450scc) 水平的增加。暴露于 B[a]P 后 P450scc 表达的上调似乎与通过 StAR 产生最大量孕烯醇酮和最少量转运胆固醇的补偿机制相关； 3β-HSD 的下调可能是因为 B[a]P 可以负面靶向 3β-HSD，而 3β-HSD 是睾酮生成所必需的。结论：B[a]P 暴露可能会降低附睾精子质量，可能是通过干扰睾酮水平来实现的，StAR 可能是 B[a]P 或其他 PAH 的主要目标类固醇生成蛋白。
Background: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells. Objective: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins. Results: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[a]P can negatively target 3β-HSD, which is required for testosterone production. Conclusions: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs.
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DOI：
10.1007/bf02629089
发表时间：
1988-06-01
期刊：
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY
影响因子：
--
作者：
KLINEFELTER, GR;EWING, LL
通讯作者：
EWING, LL
影响因子：
3.6
作者：
PAYNE, AH;YOUNGBLOOD, GL
通讯作者：
YOUNGBLOOD, GL
影响因子：
4.8
作者：
Akingbemi, BT;Sottas, CM;Hardy, MP
通讯作者：
Hardy, MP
DOI：
10.1016/s0027-5107(97)00163-2
发表时间：
1997-11-28
影响因子：
2.3
作者：
Chiang, TA;Wu, PF;Ko, YC
通讯作者：
Ko, YC
影响因子：
5.9
作者：
MATTISON, DR;PLOWCHALK, DR;MALEK, A
通讯作者：
MALEK, A