Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation.
Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation.
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2,3,7,8-四氯二苯并-对-二恶英治疗大鼠睾丸类固醇生成的抑制：证据表明关键病变发生在孕烯醇酮形成之前或期间。
DOI：
10.1016/0041-008x(90)90111-7
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发表时间：
1990
影响因子：
3.8
通讯作者：
Peterson,RE
中科院分区：
文献类型：
--
作者：
Kleeman,JM;Moore,RW;Peterson,RE
研究了2，3，7，8-四氯二苯并-对二恶英(TCDD)减少睾酮(T)分泌而不显著改变血浆黄体生成素(LH)浓度的机制。提前7天给予100μg TCDD/kg的性成熟SD大鼠的睾丸，在体外灌流类似人绒毛膜促性腺激素(HCG)时，其睾丸分泌的T比对照大鼠少30-75%。这一下降证实了睾丸对黄体生成素的反应性受到TCDD治疗的损害。黄体生成素是体内调节T分泌的激素。由于TCDD还降低了睾丸内的T含量，T分泌的减少是由于T合成的抑制，而不是由于分泌过程的失败。TCDD的这些影响并不次于营养不良，因为来自饲料限制对照组大鼠的灌流睾丸完全对hCG有反应。TCDD处理既不增加hCG刺激的任何T前体的分泌，也不显著降低睾丸将它们合成的孕烯醇酮(PREG)转化为T(PREG是最初的类固醇合成中间体)的效率。此外，当外源性PREG以大致体内的速度支持类固醇合成时，TCDD并不抑制T的分泌。我们的结论是，TCDD不能抑制PREG向T的转化。抑制T的生物合成一定是通过抑制PREG的形成来实现的。TCDD治疗显著降低了hCG灌流的睾丸分泌PREG及其代谢物的速度(在所有hCG浓度下均可见)，这一发现证实了这一结论。TCDD抑制黄体生成素hCG刺激的PREG的形成，一定是由于将胆固醇转化为PREG的酶(细胞色素P450scc)的活性降低，和/或负责将胆固醇动员到该酶的多步骤过程的损害。
The mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment decreases testosterone (T) secretion without significantly altering plasma luteinizing hormone (LH) concentrations was investigated. Testes from sexually mature Sprague-Dawley rats dosed 7 days earlier with 100 μg TCDD/kg secreted 30–75% less T than did testes from control rats when perfused in vitro with the LH analog human chorionic gonadotropin (hCG). This decrease confirms that testicular responsiveness to LH, the hormone which regulates T secretion in vivo, is impaired by TCDD treatment. Because TCDD also reduced intratesticular T content, the decrease in T secretion is due to an inhibition of T synthesis rather than to a failure of the secretion process. These effects of TCDD are not secondary to undernutrition, because perfused testes from feed-restricted control rats were fully hCG responsive. TCDD treatment neither increased the hCG-stimulated secretion of any T precursor nor significantly decreased the efficiency with which testes converted the pregnenolone (PREG) they synthesized into T (PREG is the initial steroidogenic intermediate). In addition, TCDD did not inhibit T secretion when steroidogenesis was supported by exogenous PREG at approximately the in vivo rate. We conclude that TCDD does not inhibit the conversion of PREG to T. The inhibition of T biosynthesis must instead result from an inhibition of PREG formation. The finding that TCDD treatment substantially decreased the rate at which hCG-perfused testes secreted PREG and its metabolites (a decrease seen across all hCG concentrations) confirms this conclusion. This inhibition of LH hCG -stimulated PREG formation by TCDD must be due to a reduction in the activity of the enzyme which converts cholesterol to PREG (cytochrome P450scc), and/or an impairment in the multistep process responsible for mobilizing cholesterol to this enzyme.