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Autoradiographic studies of a glucocorticoid agonist and antagonist: Localization of 3H-corticosterone and 3H-cortexolone in mouse brain

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Summary

The localization in the mouse brain of corticosterone, the natural glucocorticoid in the mouse, and cortexolone, reported to be a glucocorticoid antagonist, was studied by autoradiography 30 min after in vivo administration of the tritiated compounds.

After 3H-corticosterone (3HB) injection, radioactivity was preferentially concentrated in cell nuclei of several structures within the limbic system, and in nuclei of certain neurones of the cerebral cortex and medulla oblongata. This nuclear concentration was abolished after injection of 3H-corticosterone with an excess of unlabelled corticosterone. After 3H-cortexolone (3HS) injection, a diffuse radioactivity was observed throughout the brain. However, a higher concentration of grains was present in the ventral nucleus arcuatus and in the infundibulum. When excess unlabelled cortexolone was administered with 3H-cortexolone this preferential accumulation of grains was abolished.

The accumulation of 3H-cortexolone in the medial basal hypothalamic region suggests that cortexolone concentrates preferentially in dexamethasone (DM) target regions, and in addition the autoradiographic results show that the cortexolone-receptor complex does not accumulate in the cell nucleus.

Résumé

La localisation au niveau du cerveau de souris de la corticostérone, qui est le glucocorticoide naturel chez la souris, et de la cortexolone, démontrée comme étant un antagoniste des glucocorticoides, est étudiée par autoradiographie 30 min après injection in vivo des composés tritiés.

Après injection de 3H-corticosterone (3HB), la radioactivité se concentre préférentiellement dans des noyaux cellulaires de plusieurs structures du système limbique et dans les noyaux de certains neurones du cortex cérébral et du bulbe rachidien. Cette concentration nucléaire est abolie après injection de 3H-corticostérone en présence d'un excès de corticostérone non radioactive. Après injection de 3H-cortexolone (3HS), une distribution diffuse de la radioactivité est observée dans tout le cerveau, cependant, une concentration plus élevée de grains d'argent est présente dans la partie ventrale du nucleus arcuatus et dans l'infundibulum. Après injection de 3H-cortexolone en présence d'un excès de cortexolone non radioactive, cette accumulation préférentielle des grains est abolie.

L'accumulation de la 3H-cortexolone dans la région hypothalamique suggère que la cortexolone se concentre préférentiellement dans la région cérébrale qui contient les sites de liaison de la dexaméthasone et de plus, les résultats autoradiographiques montrent que le complexe cortexolone-récepteur ne s'accumule pas dans le noyau cellulaire.

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Coutard, M., Osborne-Pellegrin, M.J. Autoradiographic studies of a glucocorticoid agonist and antagonist: Localization of 3H-corticosterone and 3H-cortexolone in mouse brain. Cell Tissue Res. 197, 531–538 (1979). https://doi.org/10.1007/BF00233575

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