AUTHORS: Jansakova, K., Hill, M., Celarova, D., Celusakova, H., Repiska, G., Bicikova, M., Macova, L., Ostatnikova, D.<\/p>\n
ABSTRACT: The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal <\/span>changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal <\/span>development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in <\/span>prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and <\/span>sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography <\/span>tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens <\/span>synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at <\/span>augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent <\/span>with the results reported in older children, in whom the adrenal<\/span> zona reticularis<\/span> signi<\/span>fi<\/span>cantly in<\/span>fl<\/span>uences the steroid <\/span>levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex <\/span>hormones on one hand but increased anti-glucocorticoid effect of 7<\/span>\u03b1<\/span>-hydroxy-DHEA via competition with cortisone <\/span>for HSD11B1 on the other. The multivariate model found signi<\/span>fi<\/span>cant correlations between behavioral indices and <\/span>circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). <\/span>Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The <\/span>aforementioned data indicate a direction of the future research with a focus on the expression and functioning of <\/span>genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.<\/span><\/p>\n Translational Psychiatry, 2020, 10: 1-15<\/p>\n