The Inhibition of PB125I Formation in Calf Thyroid Caused by 14-Iodo-15-Hydroxy-Eicosatrienoic Acid is Due to Decreased H2O2 Availability

L. Krawiec; G. D. Chazenbalk; Susana A. Puntarulo; G. Burton; A. Boveris; Renata M. Valsecchi; M. A. Pisarev

doi:10.1055/s-2007-1010759

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 1988; 20(2): 86-90
DOI: 10.1055/s-2007-1010759

ORIGINALS

Basic
© Georg Thieme Verlag, Stuttgart · New York

The Inhibition of PB¹²⁵I Formation in Calf Thyroid Caused by 14-Iodo-15-Hydroxy-Eicosatrienoic Acid is Due to Decreased H₂O₂ Availability

L. Krawiec, G. D. Chazenbalk, Susana A. Puntarulo, G. Burton, A. Boveris, Renata M. Valsecchi, M. A. Pisarev

Division Bioquimica Nuclear, Depto. Aplicaciones Biologicas, Comision Nacional de Energia Atomica; Depto. Quimica Organica, Facultad de Ciencias Exactas y Naturales and Depto. Quimica Biologica, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina

Abstract

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Summary

Previous work from our laboratory has shown that 14-iodo-15-hydroxy-5,8,11-eicosatrienoic acid (I-HO-A) is a potent inhibitor of iodine organification in calf thyroid slices. The present studies were performed in order to clarify the mechanism of this action. Incubation of thyroid slices with 10^-4 M I-HO-A caused a 47 and 53% decrease in PB¹²⁵I formation after 30 and 60 min incubation, respectively. In a series of experiments an inverse relationship between the degree of inhibition caused by I-HO-A and total iodine content and basal iodoprotein formation was observed. Chromatographic analysis of the labeled compounds showed a significant decrease in ¹²⁵I incorporation into MIT, DIT, T₃ and total iodolipid.

The site of the inhibitory effect of I-HO-A was then sought. TPO was measured by three different methods. When TPO was solubilized from I-HO-A treated slices, no change in enzymatic activity was observed. Moreover, the same lack of action was found when solubilized TPO was incubated with I-HO-A.

The production and release of H₂O₂ into the incubation medium was measured by chemiluminiscence technique. In control slices the values increased during the first 10 min and reached a plateau. Pretreatment of the slices with 10^-4 M KI caused a 51% inhibition, while the same concentration of I-HO-A produced a 59% inhibition.

The possibility that I-HO-A might exert its action through a putative protein inhibitor was also explored. Incubation of slices with 10^-5 M I-HO-A caused a 46% decrease in PB¹²⁵I formation and addition of actinomycin D or puromycin failed to alter this effect.

The present results demonstrate that I-HO-A inhibition of ¹²⁵I organification in calf thyroid is due to a significant decrease in H₂O₂ production and add further support to the hypothesis that this compound plays a key role in thyroid autoregulation.

Key-Words

Thyroid - H₂O₂ - Iodoarachidonate - Autoregulation - Iodoprotein - TPO

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