Modulation of serum concentrations and hepatic metabolism of 17beta-estradiol and testosterone by amitraz in rats.
The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17beta-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomized (OVX) and 0.5 mg/kg E2-supplemented female rats for 7 days. E2 and metabolites were analyzed by gas chromatography-electron capture detection and testosterone and metabolites were analyzed by high-pressure liquid chromatography. In OVX and E2-supplemented females, 50 mg/kg amitraz caused an 85% decrease of serum E2 concentration and a marked increase of 2-OH-E2 concentration. Amitraz at 25 and 50 mg/kg produced 9.0-fold or greater increases of serum testosterone and 2beta-OH-testosterone levels in males. Amitraz at 25 mg/kg resulted in no or minimal increases of liver microsomal formation of E2 or testosterone metabolites. Amitraz at 50 mg/kg produced 1.4- to 3.6-fold increases of 2-OH-E2; estrone; 2beta-, 6beta-, and 16alpha-OH-testosterone; and androstenedione formation in males and intact females. Amitraz at 50 mg/kg preferentially increased intact female 16beta-OH-testosterone production by 8.6-fold. In OVX females, E2 supplement alone or cotreatment with E2 and 50 mg/kg amitraz produced 1.3- to several-fold increases of 2- and 4-OH-E2 formation and 2beta- and 16alpha-OH-testosterone production. The cotreatment increased 6beta- and 16beta-OH-testosterone formation by 1.8- and 1.6-fold, respectively. The present findings show that amitraz induces hepatic E2 and testosterone metabolism in male and female rats, decreases serum E2 concentration in OVX and E2-supplemented females, but increases serum testosterone in males.
Chou
Chen-Ping
CP
Institute of Toxicology, College of Medicine, National Taiwan University, 1 Jen Ai Road, Section 1, Taipei 100, Taiwan, ROC.
Lu
Shui-Yuan
SY
Ueng
Tzuu-Huei
TH
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010052:Ovariectomy; D010575:Pesticides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D014052:Toluidines / Q000008:administration & dosage / Q000494:pharmacology*
D052244:Endocrine Disruptors; D010575:Pesticides; D014052:Toluidines; C014983:amitraz; D013739:Testosterone; D004958:Estradiol; D051544:Cytochrome P-450 CYP3A