Assessment of rodent thyroid endocrinology: Advantages and pit-falls
In recent years, the number of commercially available rat hormone assays has increased and it is now feasible to include plasma hormone determinations as part of the toxicology safety assessment of novel compounds. This is especially true for the evaluation of the thyroid hormones. This article, which is a transcript of the lecture given to the First European Comparative Clinical Pathology Conference at Nottingham, April 1993, presents the advantages and pit-falls that an investigator must be aware of when assessing changes in plasma hormone concentrations on a toxicology study. In addition, the regulatory status of novel compounds that produce thyroid adenomas or adenocarcinomas in long-term oncogenicity studies, is discussed. Data are presented which show that the magnitude and consistency of a thyroid endocrine change, that can be expected following the administration of a compound that induces liver enzymes, is not as predictable as indicated by the literature. Hence changes in plasma thyroid hormone values may not be clearly demonstrated in rodents treated with compounds that produce thyroid tumours. This should not be of concern provided there is evidence of early follicular hypertrophy and an understanding of how the compound produces a change resulting in increased TSH drive on the thyroid gland (e.g. direct effect on the thyroid or an indirect effect via increased plasma clearance).
KeywordsRats Thyroid stimulating hormone Thyroxin Toxicology Adenomas
Unable to display preview. Download preview PDF.
- Atterwill CK, Jones C, Brown CG (1992) Thyroid gland II — Mechanisms of species-dependent thyroid toxicity, hyperplasia and neoplasia induced by xenobiotics. In: Atterwill CK, Flack JD (eds) Endocrine toxicology. Cambridge University Press, Cambridge, pp 137–182Google Scholar
- Bowman WC, Rand MJ (1980) Textbook of pharmacology, Blackwell, OxfordGoogle Scholar
- Dunn TB (1975) The unseen fight against cancer: experimental cancer research: its importance to human cancer. Bates Publishing, Charlotte, NC, 111 pp.Google Scholar
- McClain RM (1986) The role of microsomal enzyme induction in thyroid gland tumor promotion by phenobarbital. The Toxicology Forum 1986 Annual Summer Meeting, Aspen, ColoradoGoogle Scholar
- Oshima M, Ward JM (1984) Promotion of N-methyl-N-nitrosourea-induced thyroid tumours by iodine deficiency in F334/NCr rats. J Natl Cancer Inst 73:289–296Google Scholar
- Refetoff S, Reed Larsen P (1989) Transport, cellular uptake and metabolism of thyroid hormones. In De Groot L (ed.) Endocrinology Vol. 1. W.B. Saunders, Philadelphia, pp 541–561Google Scholar
- Thomas GA, Williams ED (1992) Thyroid gland I — physiological control and mechanisms of carcinogenesis. In: Atterwill CK, Flack JD (eds) Endocrine toxicology. Cambridge University Press, Cambridge, pp 137–182Google Scholar