Dehydroepiandrosterone Antagonizes Pain Stress-Induced Suppression of Testosterone Production in Male Rats.
Dehydroepiandrosterone Antagonizes Pain Stress-Induced Suppression of Testosterone Production in Male Rats.
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DOI：
10.3389/fphar.2018.00322
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发表时间：
2018
影响因子：
5.6
通讯作者：
Yao M
中科院分区：
文献类型：
--
作者：
Zhu Q;Ge F;Li X;Deng HS;Xu M;Bu T;Li J;Wang Y;Shan Y;Ge RS;Yao M
背景：间质细胞分泌类固醇激素睾酮，这是男性生育和生殖健康所必需的。应激增加糖皮质激素（大鼠体内的皮质酮）的分泌，通过直接作用于睾丸间质细胞中的受体，降低循环中的睾酮水平。睾丸内CORT水平依赖于大鼠Leydig细胞中11β-羟类固醇脱氢酶1（HSD 11B 1）对CORT的氧化失活。疼痛可能会导致压力，从而影响睾丸间质细胞中的睾酮产生。研究方法：成年雄性Sprague-Dawley大鼠在接受疼痛刺激1、3和6 h前0.5 h经口接受溶媒对照或5或10 mg/kg脱氢表雄酮（DHEA）。在本研究中，我们研究了大鼠急性疼痛诱导的应激后类固醇基因表达水平的时程变化以及DHEA预防这种变化的可能机制，测定了血浆CORT、黄体生成素（LH）和睾酮（T）水平，并测定了Leydig细胞基因表达水平。在纯化的大鼠Leydig，肝脏和大鼠Hsd 11b 1转染的COS 1细胞中检测到DHEA对HSD 11B 1催化方向的直接调节。结果如下：在疼痛刺激期间，血浆CORT水平在第1、3和6小时显著增加，而血浆T水平在第3和6小时开始显著降低。疼痛诱导的应激也降低了3小时时的星星、Hsd 3b 1和Cyp 17 a1表达水平。当5和10 mg/kg的DHEA口服给药大鼠开始疼痛刺激前0.5小时，DHEA防止疼痛介导的血浆T水平和星星，Hsd 3b 1，Cyp 17 a1的表达下降，而不影响血浆CORT水平。DHEA通过增加HSD 11 B1的氧化活性和降低其还原活性来调节HSD 11 B1的活性，从而降低Leydig细胞内CORT水平。结论：急性疼痛应激可通过上调皮质酮水平抑制睾丸间质细胞T细胞生成。DHEA可以通过调节HSD 11B 1活性来预防过量皮质酮的负面影响。
Background: Leydig cells secrete the steroid hormone, testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid [corticosterone, (CORT) in rats] that decreases circulating testosterone levels in part through a direct action on its receptors in Leydig cells. Intratesticular CORT level is dependent on oxidative inactivation of CORT by 11β-hydroxysteroid dehydrogenase 1 (HSD11B1) in rat Leydig cells. Pain may cause the stress, thus affecting testosterone production in Leydig cells. Methods: Adult male Sprague–Dawley rats orally received vehicle control or 5 or 10 mg/kg dehydroepiandrosterone (DHEA) 0.5 h before being subjected to pain stimulation for 1, 3, and 6 h. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute pain-induced stress in rats and the possible mechanism of DHEA that prevented it. Plasma CORT, luteinizing hormone (LH), and testosterone (T) levels were measured, and Leydig cell gene expression levels were determined. The direct regulation of HSD11B1 catalytic direction by DHEA was detected in purified rat Leydig, liver, and rat Hsd11b1-transfected COS1 cells. Results: Plasma CORT levels were significantly increased at hour 1, 3, and 6 during the pain stimulation, while plasma T levels were significantly decreased starting at hour 3 and 6. Pain-induced stress also decreased Star, Hsd3b1, and Cyp17a1 expression levels at hour 3. When 5 and 10 mg/kg DHEA were orally administered to rats 0.5 h before starting pain stimulation, DHEA prevented pain-mediated decrease in plasma T levels and the expression of Star, Hsd3b1, and Cyp17a1 without affecting plasma CORT levels. DHEA was found to modulate HSD11B1 activities by increasing its oxidative activity and decreasing its reductive activity, thus decreasing the intracellular CORT levels in Leydig cells. Conclusion: Stress induced by acute pain can inhibit Leydig cell T production by upregulation of corticosterone. DHEA can prevent the negative effects of excessive corticosterone by modulating HSD11B1 activity.
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影响因子：
4.8
作者：
BAMBINO, TH;HSUEH, AJW
通讯作者：
HSUEH, AJW
DOI：
10.1016/0960-0760(95)00058-8
发表时间：
1995-07-01
影响因子：
4.1
作者：
AGULAR, BM;VIND, C
通讯作者：
VIND, C
影响因子：
3.6
作者：
Gu, S;Ripp, SL;Geoghegan, TE
通讯作者：
Geoghegan, TE
影响因子：
4.8
作者：
Akingbemi, BT;Sottas, CM;Hardy, MP
通讯作者：
Hardy, MP
影响因子：
4.8
作者：
KUMAR, N;DIDOLKAR, AK;SUNDARAM, K
通讯作者：
SUNDARAM, K