The Effect of Maneb, Zineb, and Ethylenethiourea on the Humoral Activity of the Pituitary-Thyroid Axis in Rat

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Abstract
Ethylenebisdithiocarbamates (EBDCs) maneb and zineb are widely used fungicides the final metabolite of which is ethylenethiourea (ETU). EBDCs distort the humoral activity of the thyroid gland, and ETU is especially active in this respect. Male Wistar rats were exposed either to exogenous (100 ng i.p.) or endogenous (+4°C) TRH stimulation. ETU (100–500 mg/kg i.p.) caused no changes in serum TSH levels whereas zineb (70–500 mg/kg i.p.) significantly decreased the bursts induced by cold or exogenous TRH. Maneb (20–200 mg/kg i.p.) significantly decreased the cold-induced TSH response while it had no effect on the TRH-stimulated TSH secretion. None of the agents caused significant changes in serum T3 or T4 levels. It seems that maneb, and zineb, but not ETU, inhibit rat TSH secretion through an action on the endogenous TRH at the hypothalamic or pituitary level. The mechanism behind this action may be the inhibition of dopamine-β-hydroxylase.