Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings
It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype. In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes...
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Wiley
2013-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2013/159810 |
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| author | Martyn A. Sharpe Taylor L. Gist David S. Baskin |
| author_facet | Martyn A. Sharpe Taylor L. Gist David S. Baskin |
| author_sort | Martyn A. Sharpe |
| collection | DOAJ |
| description | It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype. In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes from ASD subjects and controls are compared. B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings. Controls were obtained from a different cell bank. Lactate dehydrogenase (LDH) and sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction levels were measured after incubation with different concentrations of E2, DHT, and DDE. XTT/LDH ratio, representative of mitochondria number per cell, was calculated. E2, DHT, and DDE all cause “U”-shaped growth curves, as measured by LDH levels. ASD B cells show less growth depression compared to siblings and controls (P<0.01). They also have reduced XTT/LDH ratios (P<0.01) when compared to external controls, whereas siblings had values of XTT/LDH between ASD and external controls. B-lymphocytes from people with ASD exhibit a differential response to E2, DHT, and hormone disruptors in regard to cell growth and mitochondrial upregulation when compared to non-ASD siblings and external controls. Specifically, ASD B-lymphocytes show significantly less growth depression and less mitochondrial upregulation when exposed to these effectors. A mitochondrial deficit in ASD individuals is implied. |
| format | Article |
| id | doaj-art-deb3ee3330db4ec2b9ad212d1e3cb704 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-deb3ee3330db4ec2b9ad212d1e3cb7042025-02-03T05:51:43ZengWileyJournal of Toxicology1687-81911687-82052013-01-01201310.1155/2013/159810159810Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/SiblingsMartyn A. Sharpe0Taylor L. Gist1David S. Baskin2Department of Neurosurgery, The Methodist Neurological Institute, 6560 Fannin Street, Scurlock Tower 944, Houston, TX 77030, USADepartment of Neurosurgery, The Methodist Neurological Institute, 6560 Fannin Street, Scurlock Tower 944, Houston, TX 77030, USADepartment of Neurosurgery, The Methodist Neurological Institute, 6560 Fannin Street, Scurlock Tower 944, Houston, TX 77030, USAIt has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype. In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes from ASD subjects and controls are compared. B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings. Controls were obtained from a different cell bank. Lactate dehydrogenase (LDH) and sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction levels were measured after incubation with different concentrations of E2, DHT, and DDE. XTT/LDH ratio, representative of mitochondria number per cell, was calculated. E2, DHT, and DDE all cause “U”-shaped growth curves, as measured by LDH levels. ASD B cells show less growth depression compared to siblings and controls (P<0.01). They also have reduced XTT/LDH ratios (P<0.01) when compared to external controls, whereas siblings had values of XTT/LDH between ASD and external controls. B-lymphocytes from people with ASD exhibit a differential response to E2, DHT, and hormone disruptors in regard to cell growth and mitochondrial upregulation when compared to non-ASD siblings and external controls. Specifically, ASD B-lymphocytes show significantly less growth depression and less mitochondrial upregulation when exposed to these effectors. A mitochondrial deficit in ASD individuals is implied.http://dx.doi.org/10.1155/2013/159810 |
| spellingShingle | Martyn A. Sharpe Taylor L. Gist David S. Baskin Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings Journal of Toxicology |
| title | Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings |
| title_full | Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings |
| title_fullStr | Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings |
| title_full_unstemmed | Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings |
| title_short | Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings |
| title_sort | alterations in sensitivity to estrogen dihydrotestosterone and xenogens in b lymphocytes from children with autism spectrum disorder and their unaffected twins siblings |
| url | http://dx.doi.org/10.1155/2013/159810 |
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