Effects of the insecticide amitraz, an α2-adrenergic receptor agonist, on human luteinized granulosa cells

• Published in: Human reproduction (Oxford) Vol. 20; no. 11; pp. 3018 - 3025
• Main Authors: Young, Fiona M., Menadue, Margaret F., Lavranos, Tina C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2005
• Subjects: amitraz; Biological and medical sciences; Gynecology. Andrology. Obstetrics; human luteinized granulosa cells; Medical sciences; reproductive toxicology; steroid hormones; α2-adrenergic receptor; adrenergic receptor; α; reproductive toxicology; human luteinized granulosa cells; steroid hormones; amitraz; Human; α2-Adrenergic receptor; Agonist; Insecticide; Steroid hormone; Pesticides; Amitraz; α2-adrenergic receptor/amitraz/human luteimzed granulosa cells/reproductive toxicology/steroid hormones; Vertebrata; Acaricide; Granulosa cell; Toxicology; Mammalia
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dei194

BACKGROUND: Amitraz, an insecticide used to prevent tick and mite infestation of cattle, crops and dogs, is an α2-adrenergic receptor agonist that inhibits GnRH release and the ovulatory LH surge in rats. Noradrenalin, the physiological ligand for adrenergic receptors, inhibits progesterone production by IVF-derived granulosa cells, but the effects of amitraz are unknown. METHODS: Luteinized granulosa cells obtained from women undergoing ovarian stimulation were exposed to amitraz (1, 10, 50, 100 µg/ml) for 2–72 h, and to amitraz (50 µg/ml) hCG or the specific α2-adrenergic receptor antagonist yohimbine, for 6 h. Cell numbers were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide(MTT) assay and hormone production by radioimmunoassay. RESULTS: Amitraz 10 µg/ml did not affect cell numbers or estrogen production, but reduced progesterone production to 58 8% (p < 0.01, 24 h, n = 6) of control values. Amitraz (100 µg/ml) was cytotoxic and caused a corresponding reduction in hormone production. Amitraz 50 µg/ml did not affect cell numbers or estrogen production, but reduced progesterone per cell production to 82 6% of control values after 6 h. This was prevented by 0.2 mmol/l yohimbine. Exposure to amitraz 50 µg/ml for 6 h exposure abolished hCG-stimulated progesterone production but not estrogen production. CONCLUSIONS: Amitraz inhibited basal and hCG-stimulated progesterone but not estrogen production. The inhibitory action of amitraz and its antagonism by yohimbine suggest that α2- adrenergic receptors are expressed by luteinized human granulosa cells.