Abstract

The existence of extrathyroidal monoiodotyrosine (MIT) has been debated because of uncertain results from measuring serum MIT. The reason is that the isotopic and chromatographic assays used have not been sensitive enough. This investigation undertook to establish the existence of MIT in serum utilizing a radioimmunoassay (RIA), to study the physiology of serum MIT, and to discover the pharmacologic effects of exogenous MIT.

MIT-binding antibody was raised in rabbits by immunization with an MIT-porcine thyroglobulin conjugate. The antiserum bound 40% of the labeled MIT at a final dilution of 1:1000. Incubation of 100 µ1 antiserum with 50 pg [125I]MIT and an ethanol extract of serum or standard was done at 4°C, pH 7.0, for 24 hours. Then the incubation mixture was dried under nitrogen. The bound hapten was separated by goat anti-rabbit antibody. The linear logit-log displacement plots of unknowns and standards were parallel. Lowest limit of assay detection was 31 ng/dl, and mean recovery was 98%. Cross-reactivity by monoiodo-p-hydroxyphenylpropionic acid was 12%, diiodotyrosine (DIT) 0.23%, and acid was 12%, diiodotyrosine (DIT) 0.23%, and much less for other compounds. Interassay coefficient of variation was 14% and intraassay 9%.

The extrathyroidal presence of MIT was confirmed by utilizing the multiple ligand—binding RIA. Normal serum MIT levels were 213 ± 60 ng/dl. There was wide variation in a 24-hour period without diurnal pattern. There was no significant difference between male and female MIT levels, and no change throughout the menstrual cycle. Serum MIT declined with increasing age of the subjects. Levels in hypo— and hyperthyroidism were not significantly different. Thyrotropin injection caused parallel increases in MIT, DIT, triiodothyronine, and thyroxine. Thyroid venous effluent levels of 618 ± 202 ng/dl were higher than paired carotid arterial levels of 324 ± 91 ng/dl. These observations suggested thyroidal origin of circulating MIT. MIT levels in four athyrotic patients were 100-199 ng/dl. DIT infusion caused an MIT rise which paralleled but lagged one hour later than the DIT rise. These results suggested both thyroidal and non-thyroidal sources of MIT, one of which was deiodination of DIT.

Ingestion of one gram MIT caused a 1000-fold increase of serum MIT to a peak of 324 ± 52 µg/dl in women, and 219 ± 70 µg/dl in men 30 min later, and the physiologic t½ was 45 min. MIT stimulated prolactin (PRL) a peak of 170 ± 51 ng/ml in women and 90 ± 6 ng/ml in men 30 min after the MIT peak, i.e. at 60 min after MIT ingestion. At 90 min LH drooped slightly to its nadir of 6.2 ± 2.1 mU/ml. Growth hormone, FSH, TSH, and ACTH were unchanged. Dopamine infusion or L-dopa pretreatment suppressed the MIT effect. TRH exaggerated the PRL peak, and chlorpromazine slowed the post-peak decline. MIT increased aldosterone levels. Dopamine infusion abolished this rise. After 10-day MIT administration, aldosterone levels were higher (22 ± 7.4 ng/dl) and hypokalemia (3.2 ± 0.6 mM/1) occurred. Blood pressure and peripheral norepinephrine and epinephrine levels were unchanged. Plasma renin activity did not change, but saline infusion lowered the aldosterone levels. These results suggest that dopamine synthesis inhibition is the etiology of PRL and aldosterone stimulation. MIT is a tyrosine hydroxylase inhibitor.

DIT, another tyrosine hydroxylase inhibitor, could also increase PRL and aldosterone levels. Intravenous infusion of DIT (50 µg/h) raised PRL to a mean peak plateau of 140 ng/ml, and aldosterone to 12 ng/dl. Dopamine also abolished this rise.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate School

First Advisor

R. Bruce Wilcox

Second Advisor

John E. Lewis

Third Advisor

Charles W. Slattery

Fourth Advisor

U. D. Register

Fifth Advisor

John Leonora

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1984

Date (Title Page)

8-1984

Language

English

Library of Congress/MESH Subject Headings

Thyroid Gland; Iodotyrosine -- physiology; Iodotyrosine -- pharmacodynamics; Iodotyrosine -- anatgonists & inhibitors.

Type

Dissertation

Page Count

vii; 92 p.

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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