In this study we found that the ultraviolet sunscreen component 3-(4-methylbenzylidine)camphor (4MBC) is uterotrophic in immature rats when administered by either subcutaneous injection or oral gavage. These data confirm earlier reports of uterotrophic activity for this agent when administered to immature rats in the diet or by whole-body immersion; however, they are in contrast to negative unpublished immature rat uterotrophic assay results. Data also indicate that 4MBC binds to isolated rat uterine estrogen receptors and shows activity in a human estrogen receptor yeast transactivation assay; however, we considered both of these effects equivocal. In this study, we confirmed the original observation that 4MBC was active as a mitogen to MCF-7 breast cancer cells. We evaluated and discounted the possibility that the estrogenic activity of 4MBC is related to its bulky camphor group, which is of similar molecular dimensions to that of the weak estrogen kepone. Uncertainty remains regarding the mechanism of the uterotrophic activity of 4MBC.
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http://dx.doi.org/10.1289/ehp.02110533 | DOI Listing |
Chem Biol Interact
January 2025
Department of Food Science and Biotechnology, Andong National University, Andong, 36729, Republic of Korea. Electronic address:
Prenylation, which involves the addition of hydrophobic molecules, is considered to enhance the bioavailability and biological activity of flavonoids. However, the effect of prenylation on the estrogenic activity of flavonoids with different structures remains unclear. This study evaluated the estrogen receptor-α (ER-α) agonistic and antagonistic activities of estrogenic flavonoids in both unprenylated and prenylated forms using OECD standardized in vitro ER-α transactivation assay and in vivo uterine hypertrophy assay.
View Article and Find Full Text PDFToxicol In Vitro
October 2024
College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea. Electronic address:
Estrogen receptor (ER) and androgen receptor (AR) transactivation assays for the benzophenone compounds (BPs) were performed using hERα-HeLa-9903 cells for ER and MMTV/22Rv1_GR-KO cells for AR. Results showed that some BPs, such as BP-1, BP-2, 4OH-BP, 4DHB, and 4-MBP, showed agonistic activity on ER with a higher RPCmax than 1 nM 17-β estradiol. The other BPs (BP, BP-3, BP-6, BP-7, and BP-8) showed low RPCmax in accordance with the OECD Test guideline (TG) 455 criteria, with BP-4 as the only ER-negative.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
June 2024
Pharmaceutics and Pharmacology, The Ohio State University, United States
Estrogen receptors are essential pharmacological targets for treating hormonal disorders and estrogen-dependent malignancies. Selective activation of estrogen receptor (ER) β is hypothesized to provide therapeutic benefit with reduced risk of unwanted estrogenic side-effects associated with ERα activity. However, activating ERβ without activating α is challenging due to the high sequence and structural homology between the receptor subtypes.
View Article and Find Full Text PDFJ Ginseng Res
May 2024
Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon, Republic of Korea.
Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats.
View Article and Find Full Text PDFToxics
February 2024
Reproductive and Developmental Toxicology Branch, Public Health Integrated Toxicology Division, Center for Public Health and Environmental Assessment, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Various PFAS have been identified as potential endocrine-disrupting chemicals due to estrogen receptor activation, impacts on puberty timing, or impacts on hormonally sensitive endpoints in fish. This study screened multiple PFAS in the rat uterotrophic assay to determine potential estrogenic effects on the uterus with PFAS exposure. This study also explored PFAS-dependent uterine signaling with an osmotic stress mRNA gene expression array.
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