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Outline
With the advancement of industrialization in modern society, exposure to endocrine disrupting chemicals (EDCs) in daily environments is increasingly prevalent. These substances can interfere with physiological functions by activating nuclear receptors. The constitutive androstane receptor (CAR), a crucial member of the nuclear receptor family, serves as a key regulator in detoxifying endogenous substances and sensing exogenous EDCs, participating in the regulation of drug-metabolizing enzyme expression and energy metabolism. This study employed TCPOBOP (TC), a highly specific and potent agonist of CAR, to investigate the impact of exogenous EDC-activated nuclear receptors on mammary gland development and estrogen homeostasis in pubertal female mice. Using 3-week-old female mice as models, TC was administered via intraperitoneal injection at 0.5 mg·kg-1 twice weekly. Mammary gland developmental morphology was observed, and serum estrogen levels were measured (all animal experiments conducted in this study were approved by the Institutional Animal Care and Use Committee of the Animal Experiment Center of Wuhan University, ethics number: WAEF-2023-0077). Results demonstrated that TC exposure significantly inhibited the developmental progression of the mammary ductal system through CAR activation. The underlying mechanism involved downregulating the expression of key estrogen-synthesizing enzymes while promoting estrogen metabolic conversion and inactivation, ultimately leading to reduced systemic estrogen levels. This study reveals the mechanism by which TC-activated nuclear receptor CAR suppresses mammary gland development and disrupts estrogen homeostasis in pubertal female mice. It provides insights for understanding how EDCs affect mammary development and endocrine balance in adolescent females via nuclear receptor pathways, and offers new research clues for exploring CAR's role in mammary development regulation.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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