Summary
Sprague-Dawley rats with 7,12-dimethylbenzanthracene (DMBA) induced mammary tumors were treated with the cyclic imide CG 603 (1-(morpholinomethyl)-4-phthalimido-piperidindione-2,6), with the androgen drostanolone-propionate (2α-methyldihydrotestosterone propionate) and with both these drugs together.
In both tumor and control animals the treatment led to a pronounced atrophy of the adrenal cortex with a reduction of cell and nuclear volume as well as with alterations of mitochondrial fine structure and an increase of lysosomal elements.
Examination of the anterior pituitary cells by means of light and electron microscopy revealed qualitative and quantitative changes: Following androgen treatment, large vesiclecells were observed which resemble the socalled adrenalectomy cells. In tumor animals with combined treatment the percentage of prolactin cells was reduced from over 30% to about 3%. In rats treated with androgen alone or with both drugs the number of secretory granules decreased in the prolactin cells. In addition, the endoplasmic reticulum seemed to be less abundant. An increased number of lysosomes was especially conspicuous following treatment with the cyclic imide.
The results indicate that tumor regression, atrophy of the adrenal cortex and reduction in the number of prolactin cells are more or less concurrent. The morphological findings would allow the conclusion that the treatment reduces the corticosteroid and prolactin levels.
Zusammenfassung
Sprague-Dawley Ratten mit 7,12-Dimethylbenzanthracen (DMBA)-induzierten Mammatumoren wurden mit dem cyclischen Imid CG 603 (1-(Morpholinomethyl)-4-phthalimido-piperidindion-2,6), dem Androgen Drostanolonpropionat (2 α-Methyldi-hydrotestosteronpropionat) und einer Kombination beider Präparate behandelt.
Die Behandlung bewirkte bei Tumor- und Kontrolltieren eine ausgeprägte Atrophie der Nebennierenrinde mit Verminderung des Zell- und Kernvolumens sowie Veränderungen der Mitochondrieninnenstruktur und eine Zunahme lysosomaler Einschlüsse.
Im Zellbild des Hypophysenvorderlappens ergeben sich lichtund elektronenmikroskopisch qualitative und quantitative Verschiebungen: Nach Androgenbehandlung sind gro\e Vesikelzellen zu beobachten, die den sog. Adrenalektomiezellen ähneln. Bei kombiniert behandelten Tumortieren verringert sich der Prozentsatz der Prolactin-Zellen von normal über 30% auf etwa 3%. In den Prolactin-Zellen androgenund kombinationsbehandelter Ratten sind weniger Sekretgranula vorhanden, ebenso scheint die Ausdehnung des endoplasmatischen Reticulum vermindert. Eine Zunahme der Lysosomenzahl trifft man vor allem nach Behandlung mit dem cyclischen Imid.
Aus den Ergebnissen geht hervor, da\ Tumorregression, Nebennierenrindenatrophie und Verminderung der Prolactin-Zellzahl in etwa parallel laufen. Die morphologischen Befunde deuten darauf hin, da\ Corticosteroid- und Prolactinspiegel durch die angewandte Behandlung erniedrigt werden.
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Herrn Prof. Dr. G. Wolf-Heidegger zum 60. Geburtstag gewidmet.
Mit dankenswerter Unterstützung durch das Landesamt für Forschung NRW.
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Hagen, E., Wittkowski, W. & Stöhr, P.A. Morphologische Veränderungen an Hypophyse und Nebenniere der Ratte nach Gabe hormonell wirksamer substanzen zur Behandlung von DMBA-induzierten Mammatumoren. Z. Krebsforsch. 76, 97–112 (1971). https://doi.org/10.1007/BF00284421
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DOI: https://doi.org/10.1007/BF00284421