Morfologia dos tumores de hipofise em ratos

Mennel, H. D.; Bücheler, J.; Coutinho, L. M. Barbosa; Wechsler, W.; Zülch, K. J.

doi:10.1590/S0004-282X1977000400001

Resumos

Foram analisados histologicamente 81 casos de adenomas de hipófise em ratos. Esses tumores foram observados em experimentos com carcinógenos de absorção. Essas substâncias produziram também outros tumores intracranianos. Um dos adenomas de hipófise assim obtido foi transplantado subcutaneamente, obtendo-se muitas passagens que foram seguidas histologicamente e ao microscópio eletrônico. Esses tumores foram também explantados "in vitro".

Pituitary tumors in rats can be induced by estrogens. They also occur spontaneously in various frequencies depending on strain, sex and age of the animals. They were considered to be hormone-dependent (mammotropic). However, morphologically they were mostly described as chromophobe pitutary adenomas. This does not contradict hormonal activity if one assumes that a degranulation during this activity in tumor cells takes place. METHODS: 81 pituitary adenomas were analysed histologically. They had been observed during experiments with resorptive carcinogens which either produced tumors in the intracranial cavity or were supposed to do so. One tumor was transplanted subcutaneously. Several passages of this tumor were followed up histologically and by electron-microscopy. In addition, these tumors were explanted in vitro. RESULTS: Pituitary adenomas were found in rats which were 623 ± 200 days old; 74 were females, 5 were male. The morphology of rat pituitary tumors was characterized by two cells types: the one consisted of small dark cells that were considered to be stromal elements; the other cells, the true adenoma cells, were epithelial elements in which no specific granulations could be found with the usual methods. Only few tumors had mitoses, infiltrative growth and celular pleomorphism. Tumors were rich in vasculature. Transplanted tumors grew regularly in isogenic rats. The induction time was over 200 days in the first six and about 150 days in the 7 th-10 th passages. Histologically, these tumors were not different from the primary adenomas. In parts, the stromal participation was more pronounced. By electron microscopy highly differentiated cells could be identified. They had many mitochondria, endoplasmic reticulum, vesicles and dispersed hormone granula. Some cells had a very high number of mitochondria, thus resembling oncocytes. The explantation of transplant pituitary adenomas was not successful. Fibroblasts always overgrew the adenoma cells, which had apparently a very low proliferation rate. These tumors probably are hormone-dependent and hormonally active. They can be considered to be spontaneous tumors in rats. However, they exhibited autonomous growth potentialities when transplanted into other hosts. These are benign tumors which have possibility of malignant growth.

Morfologia dos tumores de hipofise em ratos

The morphology of rat pituitary adenomas

H. D. Mennel^I; J. Bücheler^I; L. M. Barbosa Coutinho^II; W. Wechsler^I; K. J. Zülch

^IPesquisadores do Instituto ex-bolsistas do Deutscher Akademischer Austauschdienst

^IIAuxiliar de Ensino no Departamento de Patologia da Fundação Faculdade Católica de Medicina de Porto Alegre, RS

RESUMO

Foram analisados histologicamente 81 casos de adenomas de hipófise em ratos. Esses tumores foram observados em experimentos com carcinógenos de absorção. Essas substâncias produziram também outros tumores intracranianos. Um dos adenomas de hipófise assim obtido foi transplantado subcutaneamente, obtendo-se muitas passagens que foram seguidas histologicamente e ao microscópio eletrônico. Esses tumores foram também explantados "in vitro".

SUMMARY

Pituitary tumors in rats can be induced by estrogens. They also occur spontaneously in various frequencies depending on strain, sex and age of the animals. They were considered to be hormone-dependent (mammotropic). However, morphologically they were mostly described as chromophobe pitutary adenomas. This does not contradict hormonal activity if one assumes that a degranulation during this activity in tumor cells takes place.

METHODS: 81 pituitary adenomas were analysed histologically. They had been observed during experiments with resorptive carcinogens which either produced tumors in the intracranial cavity or were supposed to do so. One tumor was transplanted subcutaneously. Several passages of this tumor were followed up histologically and by electron-microscopy. In addition, these tumors were explanted in vitro.

RESULTS: Pituitary adenomas were found in rats which were 623 ± 200 days old; 74 were females, 5 were male. The morphology of rat pituitary tumors was characterized by two cells types: the one consisted of small dark cells that were considered to be stromal elements; the other cells, the true adenoma cells, were epithelial elements in which no specific granulations could be found with the usual methods. Only few tumors had mitoses, infiltrative growth and celular pleomorphism. Tumors were rich in vasculature. Transplanted tumors grew regularly in isogenic rats. The induction time was over 200 days in the first six and about 150 days in the 7 ^th-10 ^th passages. Histologically, these tumors were not different from the primary adenomas. In parts, the stromal participation was more pronounced.

By electron microscopy highly differentiated cells could be identified. They had many mitochondria, endoplasmic reticulum, vesicles and dispersed hormone granula. Some cells had a very high number of mitochondria, thus resembling oncocytes.

The explantation of transplant pituitary adenomas was not successful. Fibroblasts always overgrew the adenoma cells, which had apparently a very low proliferation rate.

These tumors probably are hormone-dependent and hormonally active. They can be considered to be spontaneous tumors in rats. However, they exhibited autonomous growth potentialities when transplanted into other hosts. These are benign tumors which have possibility of malignant growth.

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Trabalho realizado no Instituto Max Planck para pesquisas cerebrais (Diretor: Prof. Dr. Klaus Joachim Zülch) Colônia. Alemanha.

Max Planck Institut für Himforschung - Abteilung Allgemeine Neurologie - Ostmerheimerstr. 200 - 5 Köln-Merheim - Deutschland.

1. BEATSON, G. T. - On the treatment of inoperable cases of carcinoma of the mama. Suggestion for a new method of treatment, with illustrative cases. Lancet 2:104, 1896
2. BIELSCHOWSKY, F. - Functional acidophilic tumors of the pituitary of the rat. Brit. J. Cancer (London) 8:154, 1954.
3. BRYAN, W. R.; KLINCK, G. H. Jr. & WOLFE, J. M. - The unusual occurrence of a high incidence of spontaneous mammary tumors in Albany strain of rats Amer. J. Cancer 33:370, 1938.
4. BÜNGELER, W. - Die Definition des Geschwulstbegriffs und die Abgrenzung der Hyperpiasien gegenüber den Geschwüisten. Verch. dtsch. Ges. Path. 35:10, 1951.
5. CRAMER, W. & HORNING, E. S - Experimental production by oestrin of pituitary tumors with hypopituitarism and of mammary cancer. Lancet 1:247, 1936.
6. DRUCKREY, H.; SCHAGEN, B. & IVANKOVIC, S. - Erzeugung neurogener Malignome durch einmalige Gabe von Äthylnitrosoharnstoff(ÄNH) an neugeborene und jung BD-IX-Ratten. Z. Krebsforsch. 74:141, 1970.
7. DRUCKREY, H.; PREUSSMANN, R.; IVANKOVIC, S. & SCHMÂHL, D. - Organonotrope carcinogene Wirkung bei 65 verschiedenen N-Nitrosoverbindungen an BD-Ratten. Z. Krebsforsch. 69_:103, 1967.
8. McEUEN, H.; SELYE, S. & COLLIP, J. B. - Some effects of prolonged administration of oestrin in rats. Lancet 1:775, 1936.
9. FAHLBUSCH, R. - Endocrinology of pituitary tumors. Proc. German Society of Neurosurg., Hamburg, 1972. In Modern Aspects of Neurosurgery, Excerpta Medica, Amsterdam. 1973, pags. 90-95.
10. FURTH, J.; CLIFTON, K. H.; GADSDEN, E. L. & BUFFETT, R. F. - Dependent and autonomous mammotropic pituitary tumors in rats: their somatotropic features. Cancer Res. 16:608, 1956.
11. GLOW, P. H. - Incidence of chromophobe adenoma after chronic diisopropyl-fluorophosphate poisoning. Nature 221:1265, 1969.
12. GRIEPENTROG, F. - Sporitane Hypophysentumoren als häufiger Befund bei weissen Laboratoriumratten. Beitr. path. Anat. 130:40, 1964.
13. McGUIRE, W. L.; CHAMNESS, G. C; COSTLOW, M. E. & SHEPHERD, R. E. - Hormone dependence in breast cancer. Metabolism 23:75, 1974.
14. HAGUENAU, F. & LACOUR, F. - Cytologic electronique de tumeurs hypophysaires experimentales, leur appareil de Golgi. In Fine Structures of Cells. VIII International Congress of Cell Biol., Leiden (1954), Union Inter, de Science Biologique, Series B, Nr. 21(1955), pags. 316-321 (Groningen).
15. IGLESIAS-ROZAS, I. R. & CERVOS NAVARRO, J. - Ultrastructural study of human pituitary adenoma. Paper presented at the VII ^th International Congress of Neuropathology, 1-7 September, 1974.
16. ITO, A.; MARTIN, J. M.; GRINDELAND, R. E.; TAKIZAWA, S. & FURTH, J. - Mammotropic and somatotropic hormones in sera of normal rats and in rats bearing primary and grafted pituitary tumors. Int. J. Cancer 7:416,1971.
17. IVANKOVIC, S. - Selektive Erzeugung von Geschwüisten im Gehirn und Nerven-system. Krebsforsch. u. Krebskämpf. Band IV. Urban & Schwarzenberg, Mtinchen-Berlin-Wien, 1967.
18. LANDOLT, A. M. - The oncocytoma, a new histological type of pituitary adenoma. Excerpta med. (Amsterdam) 4:116, 1973.
19. MENNEL, H. D. - Zur Morphologie der Hypophysentumoren bei der Ratte. Arzneimittelforsch. 19:1955, 1969.
20. MÜLLER, W. - Zur Frage der hypophysäre Tumoren von Mischtyp. Acta Neurovegetative (Wien) 8:451, 1954.
21. MÜLLER, W. - Pathologie der Hypophysentumoren. In Öostrogene Hypophysen-tumoren. XV Symposium der Deutschen Gesellschaft für Endokrinologie, pags. 206-222. Herausgeber: J. Kracht. Springer Verlag, Berlin-Heidelberg-New York, 1969.
22. OBERLING, Ch.; GUERIN, M. & GUERIN, P. - La production expérimentale de tumeurs hypophysaires chez le rat. Compt. rend. Soc. de Biol. 123:1152, 1936.
23. SAXTON, J. A. - The relation of age to the occurrence of adenoma-like lesions in the rat hypophysis and to their growth after transplantation. Cancer Res. 1:277, 1941.
24. SONNENSCHEIN, C; RICHARDSON, I. & TASHJIAN, A. H. Jr. - Chromosomal analysis, organ specific function and appearance of six clonal strains of rat pituitary tumor cells. Exptl. Cell Res. 61:121, 1970.
25. TASHJIAN, A. Jr.; BANCROFT, F. C. & LEVINE, L. - Production of both prolactin and growth hormone by clonal strains of rat pituitary tumor cells. J. Cell. Biol. 47:61, 1970.
26. TIBOLDI, T. - Zum Problem des experimentellen Hypophysentumoren nach Östrogenbehandlung. Med. Monatsschr. 24:109, 1970.
27. WECHSLER, W. & HOSSMANN, K. A. - Elektronenmikroskopische Untersuchungen chromophober Hypophysen-Adenome des Menschen. Z. Neurochir. 26:105, 1965.
28. WEIL, A. & ZONDEK, B. - The histopathology of the pituitary of the white rat injected with follicular hormone. Endocrinology 25:114, 1939.
29. ZÜLCH, K. J. - Biologie und Pathologie der Hirntumoren. In Handbuch der Neurochirurgie, Band 13, Springer Verlag, Heidelberg, 1956.
30. ZÜLCH, K. J. & MENNEL, H. D. - Neuroblastom, Medulloblastom, Neuroepitheliom, Medulloepitheliom. In Vorbereitung.

Datas de Publicação

Publicação nesta coleção
30 Ago 2012
Data do Fascículo
Dez 1977

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BEATSON, G. T. - On the treatment of inoperable cases of carcinoma of the mama. Suggestion for a new method of treatment, with illustrative cases. Lancet 2:104, 1896

[2] 2. BIELSCHOWSKY, F. - Functional acidophilic tumors of the pituitary of the rat. Brit. J. Cancer (London) 8:154, 1954.

[3] 3. BRYAN, W. R.; KLINCK, G. H. Jr. & WOLFE, J. M. - The unusual occurrence of a high incidence of spontaneous mammary tumors in Albany strain of rats Amer. J. Cancer 33:370, 1938.

[4] 4. BÜNGELER, W. - Die Definition des Geschwulstbegriffs und die Abgrenzung der Hyperpiasien gegenüber den Geschwüisten. Verch. dtsch. Ges. Path. 35:10, 1951.

[5] 5. CRAMER, W. & HORNING, E. S - Experimental production by oestrin of pituitary tumors with hypopituitarism and of mammary cancer. Lancet 1:247, 1936.

[6] 6. DRUCKREY, H.; SCHAGEN, B. & IVANKOVIC, S. - Erzeugung neurogener Malignome durch einmalige Gabe von Äthylnitrosoharnstoff(ÄNH) an neugeborene und jung BD-IX-Ratten. Z. Krebsforsch. 74:141, 1970.

[7] 7. DRUCKREY, H.; PREUSSMANN, R.; IVANKOVIC, S. & SCHMÂHL, D. - Organonotrope carcinogene Wirkung bei 65 verschiedenen N-Nitrosoverbindungen an BD-Ratten. Z. Krebsforsch. 69_:103, 1967.

[8] 8. McEUEN, H.; SELYE, S. & COLLIP, J. B. - Some effects of prolonged administration of oestrin in rats. Lancet 1:775, 1936.

[9] 9. FAHLBUSCH, R. - Endocrinology of pituitary tumors. Proc. German Society of Neurosurg., Hamburg, 1972. In Modern Aspects of Neurosurgery, Excerpta Medica, Amsterdam. 1973, pags. 90-95.

[10] 10. FURTH, J.; CLIFTON, K. H.; GADSDEN, E. L. & BUFFETT, R. F. - Dependent and autonomous mammotropic pituitary tumors in rats: their somatotropic features. Cancer Res. 16:608, 1956.

[11] 11. GLOW, P. H. - Incidence of chromophobe adenoma after chronic diisopropyl-fluorophosphate poisoning. Nature 221:1265, 1969.

[12] 12. GRIEPENTROG, F. - Sporitane Hypophysentumoren als häufiger Befund bei weissen Laboratoriumratten. Beitr. path. Anat. 130:40, 1964.

[13] 13. McGUIRE, W. L.; CHAMNESS, G. C; COSTLOW, M. E. & SHEPHERD, R. E. - Hormone dependence in breast cancer. Metabolism 23:75, 1974.

[14] 14. HAGUENAU, F. & LACOUR, F. - Cytologic electronique de tumeurs hypophysaires experimentales, leur appareil de Golgi. In Fine Structures of Cells. VIII International Congress of Cell Biol., Leiden (1954), Union Inter, de Science Biologique, Series B, Nr. 21(1955), pags. 316-321 (Groningen).

[15] 15. IGLESIAS-ROZAS, I. R. & CERVOS NAVARRO, J. - Ultrastructural study of human pituitary adenoma. Paper presented at the VII ^th International Congress of Neuropathology, 1-7 September, 1974.

[16] 16. ITO, A.; MARTIN, J. M.; GRINDELAND, R. E.; TAKIZAWA, S. & FURTH, J. - Mammotropic and somatotropic hormones in sera of normal rats and in rats bearing primary and grafted pituitary tumors. Int. J. Cancer 7:416,1971.

[17] 17. IVANKOVIC, S. - Selektive Erzeugung von Geschwüisten im Gehirn und Nerven-system. Krebsforsch. u. Krebskämpf. Band IV. Urban & Schwarzenberg, Mtinchen-Berlin-Wien, 1967.

[18] 18. LANDOLT, A. M. - The oncocytoma, a new histological type of pituitary adenoma. Excerpta med. (Amsterdam) 4:116, 1973.

[19] 19. MENNEL, H. D. - Zur Morphologie der Hypophysentumoren bei der Ratte. Arzneimittelforsch. 19:1955, 1969.

[20] 20. MÜLLER, W. - Zur Frage der hypophysäre Tumoren von Mischtyp. Acta Neurovegetative (Wien) 8:451, 1954.

[21] 21. MÜLLER, W. - Pathologie der Hypophysentumoren. In Öostrogene Hypophysen-tumoren. XV Symposium der Deutschen Gesellschaft für Endokrinologie, pags. 206-222. Herausgeber: J. Kracht. Springer Verlag, Berlin-Heidelberg-New York, 1969.

[22] 22. OBERLING, Ch.; GUERIN, M. & GUERIN, P. - La production expérimentale de tumeurs hypophysaires chez le rat. Compt. rend. Soc. de Biol. 123:1152, 1936.

[23] 23. SAXTON, J. A. - The relation of age to the occurrence of adenoma-like lesions in the rat hypophysis and to their growth after transplantation. Cancer Res. 1:277, 1941.

[24] 24. SONNENSCHEIN, C; RICHARDSON, I. & TASHJIAN, A. H. Jr. - Chromosomal analysis, organ specific function and appearance of six clonal strains of rat pituitary tumor cells. Exptl. Cell Res. 61:121, 1970.

[25] 25. TASHJIAN, A. Jr.; BANCROFT, F. C. & LEVINE, L. - Production of both prolactin and growth hormone by clonal strains of rat pituitary tumor cells. J. Cell. Biol. 47:61, 1970.

[26] 26. TIBOLDI, T. - Zum Problem des experimentellen Hypophysentumoren nach Östrogenbehandlung. Med. Monatsschr. 24:109, 1970.

[27] 27. WECHSLER, W. & HOSSMANN, K. A. - Elektronenmikroskopische Untersuchungen chromophober Hypophysen-Adenome des Menschen. Z. Neurochir. 26:105, 1965.

[28] 28. WEIL, A. & ZONDEK, B. - The histopathology of the pituitary of the white rat injected with follicular hormone. Endocrinology 25:114, 1939.

[29] 29. ZÜLCH, K. J. - Biologie und Pathologie der Hirntumoren. In Handbuch der Neurochirurgie, Band 13, Springer Verlag, Heidelberg, 1956.

[30] 30. ZÜLCH, K. J. & MENNEL, H. D. - Neuroblastom, Medulloblastom, Neuroepitheliom, Medulloepitheliom. In Vorbereitung.

Brasil

Brasil

Morfologia dos tumores de hipofise em ratos

The morphology of rat pituitary adenomas

Resumos

Datas de Publicação