Effects of butylated hydroxyanisole on the steroidogenesis of rat immature Leydig cells

Li, Xiaoheng; Cao, Shuyan; Mao, Baiping; Bai, Yanfang; Chen, Xiaomin; Wang, Xiudi; Wang, Ying; Li, Linxi; Lin, Han Chieh; Lian, Qingquan; Huang, Ping; Ge, Ren‐Shan

doi:10.1080/15376516.2016.1202367

Cited by 19 publications

(11 citation statements)

References 14 publications

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“…36 H295R steroidogenesis assay, as a standard evaluation procedure in endocrine disruptor screening program, allows the direct measurement of alterations in cell hormone production due to chemical stimulation. 37 Recently, Li et al 16 reported the coexposure of BHA (50 μM) and 22R−OH-cholesterol led to the decrease of T production in rat immature Leydig cells, suggesting SPAs might be involved in steroidogenesis. In this study, through the monitoring of 5 steroid hormones secreted from SPA-exposed H295R, it was found that E 2 secretion responded most sensitively to SPA exposure when compared with the other tested hormones.…”

Section: Discussionmentioning

confidence: 99%

“…12 BHA could also influence hormone homeostasis, as demonstrated by BHA-decreased testosterone production in Leydig cells and rat serum. 11,16 Similarly, BHT was reported as the potential tumor promoter, carcinogen or endocrine disruptor, 17,18 but was less estrogenic than BHA according to cell proliferation assays. 19 TBHQ was found to exert multiple toxicological effects, such as causing chromosome aberration, enhancing carcinogenic effects triggered by other chemicals, and inducing cell death through apoptosis or caspase activation.…”

Section: Introductionmentioning

confidence: 99%

“…Studies based on MCF-7 proliferation revealed that BHA was estrogenic and capable to bind to estrogen receptors (ER). , Nevertheless, uterotrophic assay and Hershberger assay showed that BHA exposure decreased uterine weights of immature female rats, suggesting its antiestrogenic activity in vivo . BHA could also influence hormone homeostasis, as demonstrated by BHA-decreased testosterone production in Leydig cells and rat serum. , Similarly, BHT was reported as the potential tumor promoter, carcinogen or endocrine disruptor, , but was less estrogenic than BHA according to cell proliferation assays . TBHQ was found to exert multiple toxicological effects, such as causing chromosome aberration, enhancing carcinogenic effects triggered by other chemicals, and inducing cell death through apoptosis or caspase activation .…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo

Yang

Song

Liu

et al. 2017

Environ. Sci. Technol.

105

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Synthetic phenolic antioxidants (SPAs) are closely correlated with human life due to their extensive usages, and increasing concerns have been raised on their biosafety. The previous controversial findings caused continuous debates on their potential endocrine disrupting effects. In the present study, four commonly used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ) and 2,2'-methylenebis(6-tert-butyl-4-methylphenol) (AO2246), were investigated for their estrogenic effects, and the results from in vitro screening assays showed SPAs themselves had negligible estrogen receptor binding affinities. Nevertheless, significant increase in E secretion was observed in H295R cells treated with SPAs, especially for BHA. The transcriptional levels of steroidogenic enzymes, including StAR, 3βHSD, CYP11B1, and CYP11B2 were up-regulated via the mediation of protein kinase A (PKA) signaling pathway. In vivo experiment confirmed that waterborne exposure to BHA disturbed E and testosterone (T) levels in zebrafish gonad, thus causing potential estrogenic effects through the regulation of hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). Accordingly, this study has provided new insights for SPA-induced endocrine disrupting effects. Considering the allowable maximum level of individual BHA or in combination with TBHQ and BHT in foodstuffs (200 mg kg), the perturbation in steroidogenesis observed for relatively low concentrations of SPAs would need more public attention.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo

Yang

Song

Liu

et al. 2017

Environ. Sci. Technol.

105

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“…In animals, synergism between BHA and BHT has caused aggravation of pulmonary toxicity [ 147 ]. BHA directly inhibits the activities of CYP17A1 and HSD3B1, and the levels of expression of Hsd17b3 and Srd5a1, resulting in diminished androgen production in Leydig cells [ 148 ].…”

Section: Adverse Effects Of Antioxidant Agentsmentioning

confidence: 99%

Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxidant Agents

Pérez-Torres

Guarner-Lans

Rubio-Ruiz

2017

IJMS

193

141

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Abstract:Reductive stress (RS) is the counterpart oxidative stress (OS), and can occur in response to conditions that shift the redox balance of important biological redox couples, such as the NAD + /NADH, NADP + /NADPH, and GSH/GSSG, to a more reducing state. Overexpression of antioxidant enzymatic systems leads to excess reducing equivalents that can deplete reactive oxidative species, driving the cells to RS. A feedback regulation is established in which chronic RS induces OS, which in turn, stimulates again RS. Excess reducing equivalents may regulate cellular signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism, and thus, contribute to the development of some diseases in which NF-κB, a redox-sensitive transcription factor, participates. Here, we described the diseases in which an inflammatory condition is associated to RS, and where delayed folding, disordered transport, failed oxidation, and aggregation are found. Some of these diseases are aggregation protein cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer's disease, and metabolic syndrome, among others. Moreover, chronic consumption of antioxidant supplements, such as vitamins and/or flavonoids, may have pro-oxidant effects that may alter the redox cellular equilibrium and contribute to RS, even diminishing life expectancy.

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“…7 After late puberty, the number of LCs doubles and the immature androgen type (mainly androstanediol) switches to T. 7 After late puberty, the expression of LC genes, including LH receptor (Lhcgr), scavenger receptor class B member 1 (Scarb1), steroidogenic acute regulatory protein (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), 3β-hydroxysteroid dehydrogenase isoform 1 (Hsd3b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), and 17β-hydroxysteroid dehydrogenase isoform 3 (Hsd17b3), 11β-hydroxysteroid dehydrogenase isoform 1 (Hsd11b1), and insulin-like 3 (Insl3), are significantly up-regulated. [8][9][10] In particular, progenitor cells (CYP11A1 + HSD11B1 À LCs) differentiate into more mature HSD11B1 + LCs. 11 The development of LCs during late puberty not only requires LH stimulation but also requires growth factors and hormones secreted by Sertoli cells (SCs), such as anti-Müllerian hormone (AMH) and desert hedgehog (DHH).…”

mentioning

confidence: 99%

Cypermethrin inhibits Leydig cell development and function in pubertal rats

Wang

Zou

et al. 2022

Environmental Toxicology

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Cypermethrin is a broad‐spectrum pyrethroid insecticide that is widely used. It may induce adverse endocrine‐disrupting effects on the male reproductive system. Whether cypermethrin can disrupt Leydig cell development and function in the late puberty remains elusive. The objective of this study was to explore the effect of cypermethrin exposure to male rats on the development and function of Leydig cells in late puberty and explore the underlying mechanism. Thirty‐six male Sprague–Dawley rats (age of 35 days) were gavaged with cypermethrin (0, 12.5, 25, and 50 mg/kg/day) from postnatal day 35–49. Cypermethrin significantly lowered serum testosterone level while elevating serum luteinizing hormone level at a dose of 50 mg/kg, without altering serum follicle‐stimulating hormone level. Cypermethrin markedly decreased CYP11A1‐positive Leydig cell number at 50 mg/kg without affecting SOX9‐positive Sertoli cell number. It significantly down‐regulated the expression of Leydig cell genes, Lhcgr, Star, Cyp11a1, and Cyp17a1 and their proteins, while up‐regulating the expression of Sertoli cell genes, Dhh and Amh, and their proteins, at doses of 12.5–50 mg/kg. In addition, cypermethrin significantly increased malondialdehyde level while lowering the expression of Sod1 and Sod2 and their proteins at 50 mg/kg. Cypermethrin markedly induced reactive oxidative species at a concentration of 200 μM and reduced mitochondrial membrane potential at 25 μM and higher concentrations after 24 h of treatment to primary Leydig cells in vitro. In conclusion, cypermethrin inhibits the development and function of Leydig cells in male rats in late puberty.

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Effects of butylated hydroxyanisole on the steroidogenesis of rat immature Leydig cells

Cited by 19 publications

References 14 publications

Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo

Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo

Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxidant Agents

Cypermethrin inhibits Leydig cell development and function in pubertal rats

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