Student Theses and Dissertations

Date of Award

1973

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

McEwen Laboratory

Abstract

Tryptophan (TP) hydroxylase activity was measured using a modification of the method developed by Ichiyama et al. (l968). The distribution of the enzyme in the rat brain was determined and found to correlate with serotonin (5-HT) distribution. Bilateral adrenalectomy resulted in a decrease enzyme activity in most areas examined with the largest drop occurring in the midbrain. A similar decrease was found in 5-HT in vivo turnover. Injection of corticosterone led to an increase both in normal and adrenalectomized rats. This increase was blocked by cycloheximide, a protein synthesis inhibitor. The midbrain enzyme activity was increased in normal rats by short term stressors--cold (50 C), ether, and electric foot-shock--which resulted in increase plasma corticosterone levels. Adrenalectomized rats showed no increase when subjected to similar stressors. 5-HT brain levels of normal but not adrenalectomized rats were also elevated following short-term cold stress. These changes in TP-hydroxylase activity were not a result of changes in endogenous L-TP levels or L-aromatic amino acid decarboxylase activity. The rapidity of the changes after cold stress, corticosterone or cycloheximide injection do not appear to result from a change in enzyme amount. This is supported by the failure of a second protein synthesis inhibitor, puromycin, from producing the same results found with cycloheximide. Evidence was found to suggest that the availability of reduced cofactors may be the controlling factor in regulating rapid changes in TP-hydroxylase activity.

Comments

A thesis submitted to the Faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

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