title: Thyroid hypertrophic effect of semotiadil fumarate, a new calcium antagonist, in rats.
abstract: We studied the effects of semotiadil fumarate (SF), a new calcium antagonist with a unique benzothiazine structure, on the thyroid gland and liver in rats and compared them with those of another calcium antagonist, nicardipine (NCD), a well-known thyroidal hypertrophic agent and microsomal enzyme inducer, phenobarbital (PB), and goitrogen propylthiouracil (PTU). In oral 2-week treatment, SF caused increases in hepatic microsomal protein levels, uridine diphosphate glucuronosyltransferase (UDPGT) activity and an increase in serum thyroid stimulating hormone (TSH) level together with decreases in serum thyroid hormone levels. These results suggest that SF accelerates peripheral disposition of thyroid hormones and subsequently stimulates secretion of TSH from the pituitary gland as a compensatory response. PB and NCD had similar effects on the thyroid gland and the liver. PTU showed obvious thyroid hyperplasia and an increase in relative liver weight. Drastic increase in TSH level was observed in the PTU-treated group together with significant decreases in serum thyroid hormone levels and an increase in hepatic UDPGT activity. Histopathologically, PTU depleted the colloids in follicles, suggesting the inhibition of thyroid hormone synthesis. SF, PB and NCD showed thyroidal hyperplasia, but the extent of the change was far more moderate than that induced by PTU. These results indicate that the effect of SF is similar to those of PB and thyroid hypertrophy seen in the oral 2-week treatment with SF, and may be caused by indirectly elevated TSH levels which resulted from the induction of hepatic UDPGT activity.
authors.affiliation: Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: T
authors.initials: T
authors.lastname: Kajimura
authors.forename: M
authors.initials: M
authors.lastname: Nomura
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000633:toxicity*; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009529:Nicardipine / Q000633:toxicity; D010634:Phenobarbital / Q000633:toxicity; D011441:Propylthiouracil / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000633:toxicity*; D013959:Thyroid Diseases / Q000139:chemically induced* / Q000473:pathology; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D002121:Calcium Channel Blockers; D013844:Thiazoles; D014284:Triiodothyronine; D011441:Propylthiouracil; D013972:Thyrotropin; D009529:Nicardipine; C064356:sesamodil; D014453:Glucuronosyltransferase; D013974:Thyroxine; D010634:Phenobarbital