Triiodothyronine binding in the adult rat brain : a compartmental model approach / Monika Brigitte Schoenhoff.

Schoenhoff, Monika Brigitte.
xx, 148 leaves : ill. ; 29 cm.

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Penn dissertations -- Bioengineering. (search)
Bioengineering -- Penn dissertations. (search)
Film autoradiograms (ARG) prepared at frequent time intervals over 48 hours after i.v. administration of high specific activity (HSA) ($\sp{125}$I) -T$\sb3$ had previously provided qualitative information regarding regional triiodothyronine (T$\sb3$) processing in rat brain. Those studies showed that hormone binding and disposal in brain are saturable processes. To describe the processes quantitatively, regional distribution, binding and metabolism of T$\sb3$ in rat brain were measured and a mathematical model developed.
Methods. Forty-five adult rats were studied in the awake state: twenty-five received HSA ($\sp{125}$I) -labeled T$\sb3$ (T$\sb3\sp*$) (trace group), the remainder received unlabeled T$\sb3$ plus the same amount of T$\sb3\sp*$ (load group). Timed arterial blood samples were taken before and at frequent intervals during the 5 hour post injection period; T$\sb3\sp*$ in the plasma was identified and quantified by paper chromatography. Brains were obtained at 5, 20, 60, 180 and 300 minutes after i.v. T$\sb3$ administration, and were sectioned for thaw-mount ARG, using simultaneously-exposed ($\sp{125}$I) labeled tissue standards. Concentrations of ($\sp{125}$I) in ARGs of cerebellum, caudate nucleus, corpus callosum, hippocampus and amygdala were measured by densitometry; intervening sections were analyzed by high pressure liquid chromatography to determine the nature and proportions of labeled tissue iodothyronines.
Results. A four compartment metabolic model representing the conversion of T$\sb3$ to diiodothyronine (T$\sb2$) and iodide describes regional T$\sb3$ deiodinative metabolism in the trace group. The dynamics of the first (intravascular) compartment were described by the T$\sb3$ plasma curve; the second compartment represented T$\sb3$ binding within the brain; the third and fourth compartments represented the metabolites generated from monodeiodinase activity, namely T$\sb2$ and iodide. In the load group, an additional compartment representing all other T$\sb3$-related processes was necessary to model central T$\sb3$ kinetics. Rate constants between compartments were determined by solving the associated differential equations.
Conclusions. Quantitative information about in vivo T$\sb3$ metabolism in the adult rat brain has been obtained using the method of compartmental modeling. This model provides a tool for evaluating normal and abnormal T$\sb3$ processing in the brain.
Supervisors: Joel H. Greenberg; Mary B. Dratman.
Thesis (Ph.D. in Bioengineering) -- Graduate School of Arts and Sciences, University of Pennsylvania, 1991.
Includes bibliography.
Local notes:
University Microfilms order no.: 91-25751.
Greenberg, Joel H., advisor.
Dratman, Mary B., advisor.
University of Pennsylvania.