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 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. © 2013 martyn a. sharpe et al.