Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells

• Published in: Journal of applied toxicology Vol. 43; no. 12; pp. 1883 - 1898
• Main Authors: Ogawa, Masahiro, Kitamoto, Junya, Takeda, Takeo, Hori, Masami, Shikano, Kisako, Yamanaka-Tanaka, Amami, Tanaka, Tomoki, Kawaguchi, Tomoya, Terada, Megumi, Tanaka, Taku
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2023
• Subjects: 17β-Estradiol; Adrenal cortex; Adrenal glands; Androgens; Aromatase; Assaying; Disruption; Endocrine disruptors; Endocrine system; Estrogens; Estrus cycle; Forskolin; Gonads; Hormones; In vivo methods and tests; mRNA; Nuclear receptors; Ovaries; Plasma levels; Prochloraz; Receptors; Sex hormones; Steroidogenesis; Testosterone; forskolin; prochloraz; steroidogenesis; Cyp19; estrous cycle; female rat; decamethylcyclopentasiloxane
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4524

Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine-disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis-related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well-known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short-term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17β-estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose-dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine-disrupting effects of chemicals on steroidogenesis in vivo.