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頁籤選單縮合
題名 | Tebuconazole Disrupted Aromatase Activity and Reduced 17β-Estradiol Concentration in Pubertal Developmental Rats=得克利干擾青春期大鼠血清中環化酶與降低雌素二醇濃度 |
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作者 | 呂水淵; 陳敏貞; 廖婧淳; 蔡韙任; | 書刊名 | 臺灣農藥科學 |
卷期 | 7 2019.12[民108.12] |
頁次 | 頁81-110 |
分類號 | 433.85 |
關鍵詞 | 甲狀腺素; 得克利; 陰道開啟; 陰莖與包皮分離; 發身大鼠; Thyroid hormone; Tebuconazole; Vaginal opening; Preputial separation; Pubertal rats; |
語文 | 英文(English) |
中文摘要 | 三唑類被全球廣泛應用於水果榖類蔬菜及花等作物,同時也被用於人類生藥治療疾病。得克利曾被報導結合其他內分泌干擾農藥如依普座、鋅錳乃浦、撲克拉及撲滅寧等誘發劑量相加性的傷害,如分娩子代死亡、性別分化異常及干擾kisspeptin神經等。得克利對大鼠青春期發育與甲狀腺功能影響仍未知,本研究乃利用美國環保署第一階段檢測疑似內分泌干擾青春期發育與甲狀腺功能影響評估指引進行,使用藥劑與劑量包括炔雌醇(5mg/kg/day, 17α-ethinyl estradiol)、得克利(15,50及150 mg/kg/day)(雌大鼠)及睪固酮(0.4 mg/kg/day, testosterone)、氟他胺(3 mg/kg/day, flutamide)、得克利(15,50及150 mg/kg/day)(雄大鼠)。投予時間分別為大鼠出生後第22至42天(雌)與23至53天(雄)。試驗結果顯示,得克利未改變青春期雌、雄大鼠器官絶對重、血清中尿素氮及肌酸肝濃度。相反地,得克利高劑量150 mg/kg/day降低青春期雌大鼠子宮與卵巢重。得克利高劑量增加青春期雄大鼠睪丸與陰莖寛度但降低前列腺、儲精囊(含與不含液)、膀胱、球海棉體肌與提睪肌等相對重。得克利在低劑量延遲陰道開啓年齡及增加陰道開啓時體重。在血清中荷爾蒙濃度影響方面,得克利降低雌大鼠血清中雌素二醇濃度但對雌雄大鼠血清中睪固酮、黃體生成素及激濾泡素等無明顯影響,得克利顯著降低雌、雄大鼠血清中環化酶活性。此外,除在15與150 mg/kg/day劑量增加雄大鼠血清中三碘甲狀腺素濃度外,大致而言,得克利對雌、雄大鼠血清中甲狀腺素、三碘甲狀腺素及激甲狀腺素濃度無明顯影響。綜上結果,本試驗推論得克利主要干擾青春期雌、雄大鼠環化酶活性但詳細作用機制仍有待進一步探討。 |
英文摘要 | Around the world, triazoles are used as fungicides for fruit, grain, vegetable, and flower production and as pharmaceuticals for the treatment of human diseases. One type of triazole, tebuconazole, has been reported to combine with other endocrine disrupting pesticides, such as expoxiconazole, mancozeb, prochloraz, and procymidone, leading to dose-additive effects that impair parturition, cause pup mortality, affect sexual differentiation, and disrupt kisspeptin neurons in rats. However, the mechanisms by which tebuconazole effects thyroid function as well as the phase of pubertal development that this compound acts upon remain unclear; therefore, this study investigated pubertal developmental and thyroid function in rats. Our experiments were in accordance with US EPA OCSPP Harmonized Test Guidelines Series Number 890. For female rats, treatments (control; 5 mg/kg/day 17α-ethinyl estradiol [EE]; or 15, 50, or 150 mg/kg/day tebuconazole) were administered daily by oral gavage from postnatal day (PND) 22 to 42. For male rats, treatments (control; 0.4 mg/kg/day testosterone propionate (TP); 3 mg/kg/day flutamide; or 15, 50, or 150 mg/kg/day tebuconazole) were administered daily by oral gavage from PND 23 to 53. Our results showed that tebuconazole did not affect absolute organ weight nor the concentrations of serum blood urea nitrogen (BUN) or creatinine in either male or female rats. In contrast, high doses of tebuconazole decreased the uterus and ovary weights of female pubertal rats, whereas in male pubertal rats, high doses of tebuconazole increased relative testis weight and penis width but decreased the relative weights of the prostate, seminal vesicle (both with and without fluid), bladder, and levator ani plus bulbocavernosus muscles (LABC). In female rats, low doses of tebuconazole also delayed the age of vaginal opening (VO) and increased rat body weight at the time that VO was first observed. Furthermore, tebuconazole significantly decreased serum 17β-estradiol (E2) but did not affect the concentrations of serum testosterone, luteinizing hormone (LH), or follicular stimulating hormone (FSH). It did, however, decrease serum aromatase activity in male or female rats. Finally, tebuconazole did not affect the concentrations of serum thyroxine (T4), thyroid stimulating hormone (TSH), or triiodothyronine (T3) at any dosage level. However, dosage levels of 15 and 150 mg/kg/day tebuconazole increased the concentration of serum T3 in male rats. Taken together, our results suggest that tebuconazole primarily inhibits aromatase (CYP19) activity in pubertal male and female rats. However, the underlying mechanism of this inhibition needs to be more comprehensively elucidated. |
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