Abstract
To analyze the inhibitory effect of thyroxine (T4) on thyroid growth, freshly obtained biopsies of human nontoxic multinodular goiter tissue from 9 patients were transplanted to nude mice. After the implantation period, thyroid growth was stimulated by either hemithyroidectomy (HT) or by administration of the goitrogen propylthiouracil (PTU), with or without simultaneous administration of T4. During the latter period,3H-thymidine was continuously administered by osmotic minipumps to label replicating cells. After processing of the tissue for autoradiography, the fraction of labeled cells (LI) was calculated.
Following HT, the fraction of labeled cells in nontoxic multinodular goiter tissue was 4.8%. T4 significantly reduced the LI to 1.0%. The goitrogen induced transplant growth, the LI varying between 28% and 61% in the different specimens. Administration of T4 resulted in lower LI in all transplants: in 5 specimens the LI was similar to control transplants. In transplants from 3 goiter specimens, however, significantly higher LI were found.
The present results show that administration of T4 significantly inhibits growth of human thyroid tissue. The effect seems, however, to vary in different specimens of nontoxic goiter, indicating a varying degree of autonomous replicating activity.
Résumé
Pour analyser l'effet inhibiteur de la thyroxine (T4) sur la croissance thyroidienne des fragments de goitre multinodulaire atoxique prélevés par biopsie ont été transplantés chez des souris nues. Après la période de transplantation la croissance thyroidienne fut stimulée soit par hémi-thyroidectomie (HT) soit par l'administration de propylthiouracile goitrigène (PTU) associée ou non à l'administration simultanée de T4. Pendant la dernière période de la3H-Thymidine fut administrée en continu par des mini-pompes pour marquer les cellules reproduites. Après avoir soumis le tissu à l'auto-radiographie la fraction de cellules marquées fut calculée.
Après hémithyroidectomie cette fraction fut de 4.8%. La thyroxine réduisit ce taux à 1%. L'agent goitrigène provoqua une croissance du transplant, le taux des cellules marquées variant de 28% à 61% en fonction des différents specimens. L'administration de thyroxine entraÎna une diminution des cellules marquées au niveau de tous les greffons. Dans 5 cas le taux de ces cellules fut identique à celui des cellules des transplants. Dans 3 cas de transplants un taux significativement plus élevé de cellules marquées fut constaté.
Ces résultats montrent que l'administration de T4 inhibe la croissance du tissu thyroidien. Cependant l'effet de la thyroxine varie en fonction des différents spécimens de goitre atoxique, ce qui indique un degré variable de l'activité autonome de la reproduction cellulaire.
Resumen
Con el propósito de analizar el efecto inhibitorio de la tiroxina (T4) sobre el crecimiento tiroideo, se trasplantaron biopsias frescas de tejido tiroideo de 9 pacientes con bocio multinodular no tóxico en ratones atímicos. Transcurrido el período de implantación se estimuló el crecimiento del trasplante por medio de la hemitiroidectomía (HT) o de la administración del agente goitrogénico propiltiouracilo (PTU) con o sin la administración simultánea de T4. En esta ultima fase del estudio se administró3H-timidina en forma continua mediante minibombas osmóticas para marcar las células en proceso de replicación. Después de procesar el tejido para auradiografía se procedió a calcular la fracción de células marcadas (LI).
Después de HT la fracción de células marcadas en el tejido multinodular no tóxico fue 4.8%. La T4 redujo en forma significativa la LI a 1.0%. En el grupo de crecimiento del trasplante inducido por el agente goitrogénico, la LI osciló entre 28% y 61% en los diversos especímenes. La administración de T4 resultó en una menor LI en todos los trasplantes: en 5 especimenes la LI fue similar a la de los trasplantes control. Sin embargo en trasplantes de 3 especímenes de bocio se hallaron valores de LI significativamente mayores.
Nuestros resultados muestran que la administración de T4 inhibe en forma significativa el crecimiento del tejido tiroideo humano. Sin embargo, el efecto parece ser variable en los diferentes especimenes de bocio no tóxico, lo cual es indicativo de grados variables de autonomía en la actividad de la replicación celular.
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This work was supported by grant no. 4482 of the Swedish Medical Research Council and grant no. 3.987-0.84 of the Swiss National Science Foundation.
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Smeds, S., Peter, H.J., Gerber, H. et al. Effects of thyroxine on cell proliferation in human multinodular goiter: A study on growth of thyroid tissue transplanted to nude mice. World J. Surg. 12, 241–244 (1988). https://doi.org/10.1007/BF01658065
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DOI: https://doi.org/10.1007/BF01658065