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Dehydroepiandrosterone Antagonizes Pain Stress-Induced Suppression of Testosterone Production in Male Rats.

ABSTRACT: 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 11?-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.

SUBMITTER: Zhu Q

PROVIDER: S-EPMC5911460 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Dehydroepiandrosterone Antagonizes Pain Stress-Induced Suppression of Testosterone Production in Male Rats.

Zhu Qiqi Q Ge Fei F Li Xiaoheng X Deng Hou-Sheng HS Xu Miao M Bu Tiao T Li Jingyang J Wang Yiyan Y Shan Yuanyuan Y Ge Ren-Shan RS Yao Ming M

Frontiers in pharmacology 20180416

<b>Background:</b> 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 stres ...[more]

PMID: 29713278

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Project description:BACKGROUND:Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and glutamine (Gln) have showed the anti-inflammatory and antioxidant properties. So the aim of this study is to investigate the effect of glutamine supplementation on PCOS rats. METHODS:Female Sprague-Dawley rats were randomly assigned into four groups (n =?10 /group), control group, PCOS group, PCOS+?0.5?g/kg Gln group and PCOS+?1.0?g/kg Gln group. All the PCOS rats were administrated with 6?mg/100?g dehydroepiandrosterone (DHEA) for 20 consecutive days, all the PCOS+Gln groups were intraperitoneal injected glutamine twice in the next morning after the last DHEA injection. All the samples were collected 12?h after the last administration. Ovarian histological examinations were analyzed and the concentration of serum hormone, inflammatory and oxidative stress factors were measured. RESULTS:There was no obvious ovarian histological change among the PCOS group and PCOS+Gln groups. All the detected inflammation factors [C-reactive protein, interleukin (IL)-6, IL-18, tumor necrosis factor] showed significantly higher in all the PCOS groups compared to the control group (P <?0.01), and were significantly decreased with the supplementation of 0.5?g/kg glutamine (P <?0.01). Concentrations of superoxide dismutase were significantly lower in all the PCOS groups (P <?0.01) compared to the control group, and increased significantly with the supplementation of 0.5?g/kg glutamine (P <?0.01). Serum concentrations of malondialdehyde, nitric oxide synthase and nitric oxide were significantly higher in PCOS group (P <?0.01) compared with the control group, and significantly decreased to the comparative levels of control group with supplementation of 0.5?g/kg glutamine (P <?0.01). CONCLUSION:There is low-grade inflammation and oxidative stress in DHEA-induced PCOS rats. The supplementation of 0.5?g/kg glutamine could effectively ameliorate the inflammation and oxidative stress conditions of PCOS.

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Dehydroepiandrosterone Antagonizes Pain Stress-Induced Suppression of Testosterone Production in Male Rats.

Publications

Dehydroepiandrosterone Antagonizes Pain Stress-Induced Suppression of Testosterone Production in Male Rats.

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