Inhibition of thyroid hormone release from cultured amphibian thyroid glands by methimazole, 6-propylthiouracil, and perchlorate.
Thyroid gland explant cultures from prometamorphic Xenopus laevis tadpoles were evaluated for their utility in assessing chemicals for thyroid hormone (TH) synthesis disruption. The response of cultured thyroid glands to bovine thyroid stimulating hormone (bTSH) and the TH synthesis inhibitors methimazole, 6-propylthiouracil, and perchlorate was determined. Thyroid glands continuously exposed for 12 days to graded concentrations of bTSH released thyroxine (T4) in a dose-dependent manner. Over time, the glands appeared to reach a constant daily rate of T4 release. This suggested that the T4 stores in the glands were initially depleted but continuous release was maintained by synthesis of new hormone. The potency of methimazole, 6-propylthiouracil, and perchlorate for inhibiting T4 release was determined using glands cotreated with a single maximally effective bTSH concentration and graded concentrations of chemical. Inhibition of T4 release was dose dependent for all three chemicals. Perchlorate was the most potent inhibitor of T4 release. Methimazole and 6-propylthiouracil exhibited lower potency than perchlorate but similar potency to each other. The IC(50) (mean ± SD) for inhibition of T4 release by the thyroid glands was 1.2 ± 0.55, 8.6 ± 1.3, and 13 ± 4.0 μM for perchlorate, 6-propylthiouracil, and methimazole, respectively. This model system shows promise as a tool to evaluate the potency of chemicals that inhibit T4 release from thyroid glands and may be predictive of in vivo T4 synthesis inhibition in prometamorphic tadpoles.
Hornung
Michael W
MW
Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota 55804, USA. hornung.michael@epa.gov
Degitz
Sigmund J
SJ
Korte
Lisa M
LM
Olson
Jessica M
JM
Kosian
Patricia A
PA
Linnum
Ann L
AL
Tietge
Joseph E
JE
D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D002417:Cattle; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D007814:Larva; D008297:Male; D008713:Methimazole / Q000633:toxicity*; D009924:Organ Culture Techniques; D010472:Perchlorates / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011441:Propylthiouracil / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism*; D014982:Xenopus laevis / Q000502:physiology*
D013956:Antithyroid Agents; D010472:Perchlorates; D008713:Methimazole; D011441:Propylthiouracil; D013972:Thyrotropin; D013974:Thyroxine; C494474:perchlorate