Use of primary canine thyroid monolayer cultures to investigate compounds that are thyrotoxic in vivo.
The identification of the mechanism of action of thyroid effects is important in safety evaluation. Accordingly, primary cultures of dog thyroid follicular cells have been used to establish a method of identifying whether compounds act directly on thyroid function. The parameters measured are the uptake and incorporation into thyroglobulin of [(125)I] inorganic iodide and the release of the thyroid hormones triiodothyronine (T3) and thyroxine (T4), determined by radioimmunoassay. Drugs, such as methimazole and aminoglutethimide, reported to have effects on normal thyroid cell biochemistry in humans, in the rat (in vivo) and in porcine thyrocytes (in vitro) have been investigated in canine cell cultures. These compounds caused reduced iodine uptake and organification in our cultures after 4 hr, contrasting with reported lack of effect on iodine uptake by aminoglutethimide-treated porcine thyrocytes in vitro. After 72 hr of treatment, effects could also be observed on T3 and T4 release. This system could be used to investigate possible direct effects of compounds on cultured thyrocytes without the complication of metabolic influence that could be present in studies in vivo.
Duffy
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Safety of Medicines, ICI Pharmaceuticals, Macclesfield, Cheshire SK10 4TG, UK.
Yarnell
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SA