Abstract
Certain system modeling and analysis methods, including identifiability analysis, were applied to the design of experiments and the processing of a posteriori humoral data for quantifying the dynamics of thyroid hormone (both T3 and T4) metabolism in sheep. Two sheep were studied: one euthyroid, and one abnormal; and several alternative hypotheses concerning system structure were tested by fitting alternative models to the resulting data. For the normal sheep, the results indicated that the plasma hormone pool contained 40% of the total T4 with 14% in liver-kidneys-gut, and 47% in muscle-skin; T3 was distributed with 12–20% in plasma, 8–18% in liver-kidneys-gut, and 62–80% in muscle-skin. Also, 40–52% of the normal sheep T3 was generated by conversion of 11–17% of the T4. Compared to the euthyroid sheep, the abnormal animal lacked T4 to T3 conversion, demonstrated a higher T3/T4 secretion rate ratio, and had plasma-liver T3 kinetics increased 2–3 times. The ranges indicated are consistent with all hypotheses tested. A number of other parameters of thyroid hormone metabolism in these sheep also were computed from the data.
Similar content being viewed by others
References
Bermudez, F., Surks, M. I., and Oppenheimer, J. H. High incidence of decreased serum triiodothyronine concentration in patients with nonthyroidal disease.Journal of Clinical Endocrinology and Metabolism 1975,41, 27.
Chopra, I. J. A radioimmunoassay for measurement of thyroxine in unextracted serum.Journal of Clinical Endocrinology and Metabolism 1972a,34, 938–947.
Chopra, I. J., Ho, R. S., and Lam, R. An improved radioimmunoassay of triiodothyronine in serum: Its application to clinical and physiological studies.Journal of Laboratory and Clinical Medicine 1972b,80, 729–739.
Chopra, I. J., Chopra, U., Smith, S. R., Reza, M., and Solomon, D. H. Reciprocal change in serum concentrations of 3,3′,5′-triiodothyronine (reverse T3) and 3,3′,5-triiodothyronine (T3) in systemic illness.Journal of Clinical Endocrinology and Metabolism 1975a,41, 1043.
Chopra, I. J., Williams, D. E., Orgiazzi, J., and Solomon, D. H. Opposite effects of dexamethasone on serum concentrations of 3,3′,5′-triiodothyronine (reverse T3) and 3,3′,5-triiodothyronine (T3).Journal of Clinical Endocrinology and Metabolism 1975b,41, 911–920.
Chopra, I. J. An assessment of daily production and significance of thyroidal secretion of 3,3′,5′-triiodothyronine (reverse T3) in man.Journal of Clinical Investigation 1976,58, 32–40.
DiStefano, J. J. III, and Fisher, D. A., Peripheral distribution and metabolism of the thyroid hormones: A primarily quantitative assessment. In J. M. Hershman and G. A. Bray (Eds.),International encyclopedia of pharmacology and therapeutics. Oxford: Pergamon, 1975.
DiStefano, J. J. III, Wilson, K. C., Jang, M., and Mak, P. H. Identification of the dynamics of thyroid hormone metabolism.Automatica 1975,11, 149–159.
Fisher, D. A., Chopra, I. J., and Dussault, J. H. Extrathyroidal conversion of thyroxine and triiodothyronine in sheep.Endocrinology 1972,91, 1141–1144.
Irvine, C. H. G. Qualitative and quantitative aspects of thyroxine metabolism in sheep.Endocrinology 1969,85, 662–673.
Irvine, C. H. G. Concentration of thyroxine in cellular and extracellular tissues of the sheep and the rates of equilibration of labeled thyroxine.Endocrinology 1974a,94, 1060–1071.
Irvine, C. H. G.A 4 compartment model of thyroxine (T4) metabolism. Paper presented at the Thyroid Metabolism Conference in Glasgow, England, in press, 1974b.
Surks, M. I., and Oppenheimer, J. H. Metabolism of phenolic-and tyrosyl-ring labeledL-thyroxine in human beings and rats.Journal of Clinical Endocrinology and Metabolism 1971,33, 612–622.
Vagenakis, A. G., Burger, A., Portnoy, G. I., Rudolph, M., O'Brian, J. T., Azizi, F., Arky, R. A., Nicod, P., Ingbar, S. H., and Braverman, L. E. Diversion of peripheral thyroxine from activating to inactivating pathways during complete fasting.Journal of Clinical Endocrinology and Metabolism 1975,41, 191.
Wilson, K. C.Thyroid hormone metabolism in sheep: a biocybernetic approach to experimentation and analysis. UCLA Ph.D. Dissertation, also UCLA Report UCLA-ENG-7611, January 1976.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wilson, K.C., DiStefano, J.J., Fisher, D.A. et al. System analysis and estimation of key parameters of thyroid hormone metabolism in sheep. Ann Biomed Eng 5, 70–84 (1977). https://doi.org/10.1007/BF02409340
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02409340