Curcumin downregulates 8-br-cAMP-induced steroidogenesis in mouse Leydig cells by suppressing the expression of Cyp11a1 and StAR independently of the PKA-CREB pathway

Lin, Yi Chun; Chiu, Chin‐Yi; Liu, Hung-Chang; Wang, Jyun-Yuan

doi:10.1507/endocrj.ej18-0010

Cited by 14 publications

(8 citation statements)

References 30 publications

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“…However, the regular curcumin was not as sensitive as CDC, and it had no significant effect on Leydig cells. These results were similar to the reported that curcumin had no impact on the basal steroidogenesis in MA-10 cells, but it could inhibit the steroidogenesis in primary mouse Leydig cells 32 . Meanwhile, the 5 μM CDC showed higher testosterone levels, and the subsequent experiments were performed in concentrations ranging from 0.1 to 5 μM.…”

Section: Discussionsupporting

confidence: 92%

The aphrodisiac potential of β-cyclodextrin–curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells

Liu

Xue

Yuan

et al. 2022

Sci Rep

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The water-soluble β-cyclodextrin–curcumin (CDC) is used in pharmaceutical applications and as a natural food colorant. The previous study revealed that curcumin potentially impacted the reproductive system. The present study investigated the possible roles of the CDC in testosterone secretion in Leydig cells and mice. Primary Leydig cells were treated with the CDC to determine their effect on cell proliferation, testosterone levels, the protein and mRNA expression of the transcription factor, and steroidogenic enzymes. Our data showed that CDC stimulated testosterone production via upregulating transcription factor steroidogenic factor-1 (NR5A1), cAMP-response element-binding protein (CREB), and steroidogenic enzymes steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), 17-alpha-hydroxylase/17,20-lyase (CYP17A1), 3β-/17β-hydroxysteroid dehydrogenase type 1 (3β/17β-HSD, HSD3b1/HSD17b1). CDC could significantly stimulate H89-suppressed StAR and CREB expression but not reverse melatonin-suppressed StAR expression. We further detected the hormonal activity with transgenic yeast, and CDC showed potential androgenic antagonistic activity. Meanwhile, we investigated its aphrodisiac effect on hydrocortisone-induced mice. Exposure to hydrocortisone decreased the mating ability, reproductive organs, and testosterone level and disrupted testicular histology. However, all of these effects were significantly improved by CDC treatment. In conclusion, these results indicated that mechanisms of CDC in stimulating testosterone production involve upregulating the cAMP-PKA pathway.

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Section: Discussionsupporting

confidence: 92%

The aphrodisiac potential of β-cyclodextrin–curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells

Liu

Xue

Yuan

et al. 2022

Sci Rep

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“…[13][14][15] Particularly, curcumin possessed the potential androgen-antagonizing property, as it could down-regulate the expression of human androgen receptors, 16 HSD17B3, 17 HSD3B2 and CYP11A1 genes, 18 as well as the mouse Cyp11a1 and StAR genes. 19 To summarize, the multifaceted bioactivities of curcumin contribute to its diverse effects on the reproductive systems. The potential reproductive toxicity of curcumin is also dependent on the dosage, preparations and delivery approaches.…”

Section: Introductionmentioning

confidence: 99%

<p>Acute Damage to the Sperm Quality and Spermatogenesis in Male Mice Exposed to Curcumin-Loaded Nanoparticles</p>

Xia

Wang

Yang

et al. 2020

IJN

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Background: Curcumin has shown many pharmacological activities in both preclinical and clinical studies. Many technologies have been developed and applied to improve the solubility and bioavailability of curcumin, especially the nanotechnology-based delivery systems. However, there has been evidence that certain nanoparticles have potential reproductive toxicity in practice. Methods: Curcumin-poly (lactic-co-glycolic acid) (PLGA)-PEG nanoparticles (Cur-PLGA-NPs for short) were prepared. The Cur-PLGA-NPs were evaluated with its effect on the proliferation of mouse testicular cell lines in vitro and spermatogenesis in vivo, while PLGA-NPs were used as control. For animal experiments, male BALB/c mice were treated with 20 mg/kg of Cur-PLGA-NPs for continuous 10 days via tail vein injection. Results: We found the curcumin nanoparticles suppressed the proliferation of testicular cell lines in vitro. Furthermore, a short-term intravenous delivery of curcumin-loaded nanoparticles could be harmful to the differentiation of spermatogonia, the elongation of spermatids, as well as the motility of mature sperms. Conclusion: In the present study, we disclosed the acute damage on mouse spermatogenesis and sperm parameters by curcumin-loaded nanoparticles. Our results suggested that the reproductive toxicity of nanoformulated curcumin needs to be prudently evaluated before its application.

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“… 2017 ; Lin et al. 2018 ). Our study showed that the mRNA expression of CYP11A1 and STAR in Leydig cells of testis was lower in the model group than in other groups, indicating that the expression of CYP11A1 and STAR was positively correlated with the testosterone production.…”

Section: Discussionmentioning

confidence: 99%

Effects of Bushen Yiyuan recipe on testosterone synthesis in Leydig cells of rats with exercise-induced low serum testosterone levels

Wang

Peng

Zhou

et al. 2022

Pharmaceutical Biology

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Context Bushen Yiyuan recipe (BYR) is an effective Chinese prescription with antifatigue and antioxidation effects. Objective The effects of BYR on testosterone synthesis in rat Leydig cells with exercise-induced low serum testosterone levels (EILST) are assessed. Materials and methods Thirty-two Sprague-Dawley rats were chronically trained for 6 weeks to establish an EILST model. EILST rats were divided into model (physiological saline), EFE (700 mg/kg ethanol extract of Epimedii folium , the dried leaves of Epimedium brevicornu Maxim [Berberidaceae]), and BYR groups (350 and 700 mg/kg) for 6 weeks. Expression of HMG-CoA, LDL-R, SR-BI, STAR and CYP11A1 were quantified by RT qPCR and Western blots. Results Compared with the model group (115.52 ± 13.05 μg/dL; 67.83 ± 14.29; 0.32 ± 0.04; 0.33 ± 0.02; 0.38 ± 0.01), serum testosterone, testosterone/cortisol ratio, HMG-CoA, STAR and CYP11A1 relative protein expression significantly increased in low-dose BYR (210.60 ± 5.08 μg/dL; 119.38 ± 13.02; 0.47 ± 0.01; 0.46 ± 0.03; 0.46 ± 0.02), high-dose BYR (220.57 ± 14.71 μg/dL; 124.26 ± 14.79; 0.49 ± 0.02; 0.42 ± 0.03; 0.51 ± 0.02), and EFE groups (206.83 ± 5.54 μg/dL; 119.53 ± 25.04; 0.45 ± 0.02; 0.42 ± 0.02; 0.41 ± 0.02) (all p < 0.01, except for CYP11A1 in EFE group). HMG-CoA, STAR and CYP11A1 mRNA relative expression significantly increased in low-dose and high-dose BYR group compared to model group (all p < 0.01). Conclusions BYR affects endogenous cholesterol synthesis and testosterone synthesis to prevent and treat EILST levels in rats. It can improve the body’s sports ability.

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Curcumin downregulates 8-br-cAMP-induced steroidogenesis in mouse Leydig cells by suppressing the expression of Cyp11a1 and StAR independently of the PKA-CREB pathway

Cited by 14 publications

References 30 publications

The aphrodisiac potential of β-cyclodextrin–curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells

The aphrodisiac potential of β-cyclodextrin–curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells

<p>Acute Damage to the Sperm Quality and Spermatogenesis in Male Mice Exposed to Curcumin-Loaded Nanoparticles</p>

Effects of Bushen Yiyuan recipe on testosterone synthesis in Leydig cells of rats with exercise-induced low serum testosterone levels

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