propylthiouracil and potassium-thiocyanate

The ability of different goitrogens (anti-thyroid agents) to induce precocious metamorphosis in larval sea lampreys (Petromyzon marinus) was assessed in four separate experiments. Two of these goitrogens (propylthiouracil [PTU] and methimazole [MMI]) are inhibitors of thyroid peroxidase-catalyzed iodination, and three (potassium perchlorate [KClO(4)], potassium thiocyanate [KSCN], and sodium perchlorate [NaClO(4)]) are anionic competitors of iodide uptake. Because, theoretically, all of these goitrogens prevent thyroid hormone (TH) synthesis, we also measured their influence on serum concentrations of thyroxine and triiodothyronine. All goitrogens except PTU significantly lowered serum TH concentrations and induced metamorphosis in some larvae. The incidence of metamorphosis appeared to be correlated with these lowered TH concentrations in that KClO(4), NaClO(4), and MMI treatments resulted in the lowest serum TH concentrations and the highest incidence of metamorphosis in sea lampreys. Moreover, fewer larvae metamorphosed in the KSCN and low-KClO(4) treatment groups and their serum TH concentrations tended to be greater than the values in the aforementioned groups. MMI treatment at the concentrations used (0.087 and 0.87 mM) was toxic to 55% of the exposed sea lampreys within 6 weeks. The potassium ion administered as KCl did not alter serum TH concentrations or induce metamorphosis. On the basis of the results of these experiments, we have made the following conclusions: (i) In general, most goitrogens other than PTU can induce metamorphosis in larval sea lampreys, and this induction is coincident with a decline in serum TH concentrations. (ii) The method by which a goitrogen prevents TH synthesis is not directly relevant to the induction of metamorphosis. (iii) PTU has variable effects on TH synthesis and metamorphosis among lamprey species. (iv) Unlike in protochordates, potassium ions do not induce metamorphosis in sea lampreys and are not a factor in the stimulation of this event.

Topics: Animals; Antithyroid Agents; Iodide Peroxidase; Iodides; Lampreys; Larva; Metamorphosis, Biological; Methimazole; Perchlorates; Potassium; Potassium Chloride; Potassium Compounds; Propylthiouracil; Sodium Compounds; Thiocyanates; Thyroid Hormones; Triiodothyronine

In order to investigate whether goitrogens and liver enzyme-inducers modify the tumorigenesis in the liver or lung, 6-week old male F344 rats were given single subcutaneous injection of DHPN, and starting one week later received water containing goitrogens, namely sulfadimethoxine (SDM), propylthiouracil (PTU) and potassium thiocyanate (KSCN), or an enzyme-inducer, phenobarbital (PB), for 19 weeks ad libitum. Although the number of GST-P positive foci in the liver was significantly increased in the PB group as compared to the control group, there were no significant fluctuations in the SDM, PTU and PB groups. With respect to the lung, it is suggested that SDM, KSCN and PB may enhance the lung tumorigenesis, since the multiplicities of hyperplasias of alveolar epithelia were increased in groups treated with these compounds.

Topics: Animals; Antithyroid Agents; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Nitrosamines; Phenobarbital; Propylthiouracil; Rats; Rats, Inbred F344; Sulfadimethoxine; Thiocyanates

Topics: Animals; Iodides; Iodine; Propylthiouracil; Rats; Thiocyanates; Thiouracil; Thyroid Gland