Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. This dataset is associated with the following publication: Karmaus , A., C. Toole, D. Filer , K. Lewis, and M. Martin. (Toxicological Sciences) High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells. TOXICOLOGICAL SCIENCES. Society of Toxicology, 150(2): 323-332, (2016).

RAW DATA, SAS FILES AND DATA MEANS. This dataset is associated with the following publication: Howdeshell, K., C. Rider, V. Wilson , J. Furr , C. Lambright , and E. Gray. Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, 148(2): 488-502, (2015).

A liquid chromatogrpahy mass spectrometry (LC-MS) method was developed for the analysis of 13 endogenous steroids. The method was validated using both fish plasma and fish holding water. The method was applied to the assessment of endocrine disruption by analyzing plasma of fathead minnows exposed to fadrozole, and by analyzing holding water from Japanese medaka exposed to fadrozole. This dataset is associated with the following publication: Blackwell, B., and G. Ankley. Simultaneous determination of a suite of endogenous steroids by LC-APPI-MS: Application to the identification of endocrine disruptors in aquatic toxicology. Journal of Chromatography B. Elsevier Science Ltd, New York, NY, USA, 1163: 122513, (2021).

metadata sheet, data sheet for each table and figure in the published manuscript. This dataset is associated with the following publication: Gray , E., J. Furr , K. Tatum-Gibbs, C. Lambright , H. Sampson, B. Hannas, V. Wilson , A. Hotchkiss , and P. Foster. Establishing the Biological Relevance of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels. TOXICOLOGICAL SCIENCES. Society of Toxicology, 149(1): 178-91, (2016).

the dataset contains NHEERL collected data on fetal male rat gestational day 18 testicular testosterone production and related data. This dataset is associated with the following publication: spade, d., C. Yue Bai , C. Lambright, J. Conley, K. Boekelheide , and E. Gray. Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells. TOXICOLOGY LETTERS. Elsevier Science Ltd, New York, NY, USA, 290: 55-61, (2018).

the data set contains the figures and tables from the publication in addition to the means, standard errors of the mean and the sample sizes used in each group for every experiment. the data set also contains a description of the genes, their function and acronyms on the QPCR arrays used in the study. Finally, the dataset includes the histopathology reports on the uterine changes induced by the different chemicals and the criteria used by the pathologist to classify the estrogenic effects of the chemicals. This dataset is associated with the following publication: Conley, J., B. Hannas, V. Wilson, E. Gray, and J. Furr. A demonstration of the uncertainty in predicting the estrogenic activity of individual chemicals and mixtures from an in vitro estrogen receptor transcriptional activation assay (T47D-KBluc) to the in vivo uterotrophic assay using oral exposure. TOXICOLOGICAL SCIENCES. Society of Toxicology, 382-395, (2016).

Background Saliva reflects the plasma free fraction of testosterone which is biologically active, and available for uptake by tissues. Testosterone concentration in saliva, though differing slightly from the concentration of unbound testosterone in serum, is in good correlation with the latter, indicating that salivary testosterone provides a reliable method for determination of serum free testosterone. The study aimed to investigate salivary testosterone levels and their changes in preadolescent children and to study sexual dimorphism. Methods Testosterone levels were determined in 203 healthy preadolescent children (77 girls and 126 boys) from saliva samples by radioimmunoassay. Sampling was performed once a year with respect to circadian and seasonal fluctuations of testosterone. Data were statistically analyzed by Statgraphic software. Results Mean salivary testosterone concentrations (± SD) were 0.038 ± 0.012 nmol/L and 0.046 ± 0.026 nmol/L for girls and boys, with the medians 0.035 nmol/L and 0.041 nmol/L, respectively. Statistical analysis did not prove changes in salivary testosterone concentrations in the preadolescent period of life, with an exception of the insignificant fall at the age of 7 years, and an insignificant rise at the age of 9 years in girls. Conclusions Generally it can be concluded that salivary testosterone levels in our prepubertal subjects remained stable. There was no significant increase of salivary testosterone levels from the age of 6 until the age of 9 in both sexes. Sexual dimorphism in salivary testosterone levels was proved with significantly higher (p = 0.009) salivary testosterone levels in boys than in girls.

Feminization of male fish and the role of endocrine-active chemicals in this phenomenon has been an area of intense study for many years. Estrone (E1), a natural steroid, is found in aquatic environments sometimes at relatively high concentrations. However, E1 has been less thoroughly studied than 17β-estradiol (E2) or 17α-ethynylestradiol due in part to a relatively lower potency in metabolically-limited estrogen receptor (ER) binding/activation assays. Recent evidence suggests that in vivo biotransformation of E1 to E2 may occur in fathead minnows (Pimephales promelas) residing in environments with high concentrations of E1, such as near wastewater treatment plants. The enzymes likely responsible for this biotransformation, 17β-hydroxysteroid dehydrogenases (17βHSDs), have been well characterized in mammals but to a lesser extent in fish species. In the current study, a novel systematic analysis of amino acid sequence data from the National Center for Biotechnology Information database demonstrated that multiple 17βHSD isoforms are conserved across different fish species. Experimentally, we showed that metabolically-active hepatic cytosolic preparations from two commercially important salmonid species, rainbow trout and lake trout, biotransformed E1 to E2 to a degree sufficient to alter results of competitive ER binding assays. These results from in silico and in vitro analyses indicate E1 and biotransformation may play a significant role in the feminization of a variety of fish species in contaminated aquatic environments. This dataset is associated with the following publication: Tapper, M., R. Kolanczyk, C. LaLone, J. Denny, and G. Ankley. Conversion of estrone to 17â-Estradiol: A potential confounding factor in assessing risks of environmental estrogens to fish. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 39(10): 2028–2040, (2020).

GEOSite dataset for article 'In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals '. This dataset is associated with the following publication: Matteo, G., K. Leingartner, A. Rowan-Carroll, M. Meier, A. Williams, M. Beal, M. Gagne, R. Farmahin, S. Wickramasuriya, A.J. Reardon, T. Barton-Maclaren, J. Corton, C. Yauk, and E. Atlas. In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 191(2): 266-275, (2023).

Screening certain environmental chemicals for their ability to interact with endocrine targets, including the androgen receptor (AR), is an important global concern. We previously developed a model using a battery of eleven in vitro AR assays to predict in vivo AR activity. Here we describe a revised mathematical modelling approach that also incorporates data from newly available assays and demonstrate that subsets of assays can provide close to the same level of predictivity. These subset models are evaluated against the full model using 1820 chemicals, as well as in vitro and in vivo reference chemicals from the literature. This dataset is associated with the following publication: Judson, R., K. Houck, K. Friedman, J. Brown, P. Browne, P. Johnston, D. Close, K. Mansouri, and N. Kleinstreuer. Selecting a Minimal set of Androgen Receptor Assays for Screening Chemicals. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 117(November 2020): 104764, (2020).