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A Study on Morphological Changes in the Testes of Old Albino Rats
Department of Experimental Pathology, Dr. Karl Thomae, GmbH, Biberach/Riss (Head: Prof. Dr. H. UEBERBERG)
A Study on Morphological Changes in the Testes of Old Albino Rats Untersuchungen tiber Hodenveranderungen bei alten Albinoratten LEHNHARD LUTZEN
and
HEINZ UEBERBERG
With 6 Figures· Received April 17, 1973 . Accepted May
II,
1973
Summary We studied the testes of 90, two year-old male albino rats. In 27 animals string-like hyperplasia of the Leydig cells were found. 49 animals showed nodular or adenomatous proliferation in one or both testes. The size varied ranging from microscopically detectable lesions to others which occupied th e entire testis. We refer to them as adenomata of the Leydi g cells. Malignant lesions were not found. In our experience the changes were not present in animals up to one year of age. No definite conclusions can be made as to the origin of these adenomata. At the moment, however, we would like to hypothesise that they a re due initially to a process induced by the pituitary and that afterwards their growth becomes autonomous. Apart from the tumour-like changes in the Leydig cells, atrophic changes in the germinal epithelium were also present, which, howeve r, appeared also in the young animals in the same form.
Many papers can be found in the literature dealing with changes-particularly tumour formation-in the testes of animals (SCHLEGEL, 1924). They seem mostly to concern the dog (KUNZE, 1922; SCHLOTTHAUER, 1938; BRAUN, 1939; INNES, 1942; SCULLY, 1952). It is surprising that virtually nothing has been published about the type and incidence of age-dependent changes in the testes of the albino rat and in particular nothing about tumours, although this species is the one most commonly used in experimental work. Presumably the reason is that animal experiments are normally carried out over a short period of time and mainly with younger fully-grown animals. RATCLIFFE (1940) found 2 tumours of the testes amongst 231 spontaneous tumours in male rats which he designated fibrosarcoma. CRAIN (1958) on the other hand found interstitial adenomata of the testes in 35 out
378 . L. LUTZEN and H. UEBERBERG
of 334 male rats aged 18-24 months. In the work of SCHARDEIN, FITZGERALD and KAUMP (1968) due to the large number of animals used the occurrence of spontaneous tumours within a strain of rats is reported, but no mention is made of the testis. Our knowledge of age-dependent changes in the testis of the rat becomes more significant with the planning of long-term experiments, as for instance is done in the testing of chemical substances for carcinogenic properties. Such investigations are carried out over a period of up to 2 years. We had the opportunity of performing a morphological investigation on a large number of old rats which had never before been used for experimental purposes. In the following work we report on our findings concerning the testis.
Material and Methods The experiments were carried out on the testes of 90 male SPF-albino rats, strain FW 49/Biberach. The average weight and age of the animals were 650 g and 2 years (720-778 days) respectively. Five rats were housed together in an SPF all wire Type III cage under SPF-conditions. Temperature and humidity were kept constant by means of a complete airconditioning system (20 o+l o C, 55-60% humidity). Alternating 12 hour periods of light and dark were maintained in the animal house. During the periods of light the illumination intensity was 150 Lux. Food: Altromin R "fortified" (steam-sterilised) and water were available ad libitum. The animals were sacrificed under anaesthesia (Nembutal - 1 ml/kg = 50 mg/kg) by slitting the aorta. The testes were treated with BOUIN'S fixing solution. The organs were embedded in Paraplast and serial sections were cut which were stained as follows:-I. HE stain; 2. Sudan black stain; 3. v. Gieson stain; 4. v. Kossa stain; 5. Azan stain; 6. PAS reaction. To identify pigments the following reaction according to KRUTSAY (1971) was carried out; 1. treatment with ammoniacal alcohol to remove precipitates caused by formalin, staining with haematoxylin-eosin ; 2. Berlin-blue reaction; 3. Lipofuscin identification; 4. bleaching with KMn0 4 ; 5. Argentaffine reaction; 6. Ferri-ferricyanide-reaction. In order to identify any crystals the prepared slices were viewed under polarised light.
Results During the post-mortem examination of our test material we were struck by the difference in size of the testes. The average weight was 4.41 g. There was, however, a wide range of variability. For instance weights ranging from 1.51 - 13.53 g were recorded. 15 of the 90 animals showed a difference in weight between the left and right testis. The colour varied in accordance with the consistency. Soft, elastic testes were mainly light yellow. In some the surface was a yellowish-brown mottled colour, and they had a firm elastic consistency. Others had a variable consistency, in which the Tunica albuginea was transparent. The testis itself was filled with an amber-coloured
Testes of Old Albino Rats' 379
Fig.
1.
Loss of the germinal epithelium with the appearance of giant-cells. HE-staining, x 205.
liquid interspersed with white threads. In a few cases firm as well as soft areas were found in one and the same testis. Histological changes in the testis were observed in 76 of the 90 animals. No anomalies nor traumatic lesions nor the sequelae of these were seen. There were two main types of changes in our test material: degenerative or atrophic signs in the tubules, and hyperplastic or tumour-like growth of the Leydig cells (L. c.). In many cases just from the macroscopic picture, and from the weight and consistency of the testis, deviations from the norm could be predicted. In some cases only one testis was involved. Atrophy of tubules could be seen 24 times in the 90 animals. In nine instances the whole testis was affected, in other instances only isolated segments. Sometimes a complete failure of spermatogenesis ensued. Often the formation of giant-cells could be seen and all manner of cell shapes and sizes. Alongside cells with a large round hyperchromatic nucleus were to be found others which were not enlarged, or simply bizarre shapes with lobular nuclei (Fig. I). In the region of the atrophic tubules the L. c. had no special peculiarities. The interstitial tissue was sometimes strongly disintegrated and filled with oedematous fluid (Fig. 2).
380 •
Fig.
2.
1. UiTZEN and H.
UEBERBERG
Atrophy of the germinal epithelium with excessive interstitial oedema. HE-staining,
x I40.
Fig. 3. String-like hyperplasia of the 1. c., intact germinal epithelium. HE-staining, X 140.
Testes of Old Albino Rats' 38I
Fig. 4. "Miliary" profile ration of the L. c. HE-staining, X I40.
On the whole, however, the proliferation of L. c. which was found in 70 out of 90 cases was the most remarkable feature. In 27 cases the L. c. were spread out in the interstices in string-like shapes (Fig. 3). Therefore, our reference to a "string-like hyperplasia" of the L. c. Generally speaking they appeared as tightly packed, strongly eosinophile-tinged polygonal cells mostly with a central cell nucleus. Degenerative changes in the germinal epithelium were not seen in the region of these L. c. hyperplasia. Spermatogenesis was unaffected. Nodular profileration varying in degree and extent was apparent in 49 animals in 4 of which only one testis was affected. States ranging from microscopically small "miliary" foci (Fig. 4) to almost complets tumour-like change of a testis were found (Fig. 5). This figure also clearly shows the multiplicity of the growth in which a conglomeration of single nodes occurs. From the histological point of view, there was no difference in cell picture between the microscopically small L. c. nodes and the string-like hyperplasia. In contrast, the cytological picture in the large nodular proliferation showed partial differentiation in the cells. The cytoplasm was no longer as dense and did not have the strong eosinophile staining, but had a more honeycomb-like structure. Sometimes the cell nucleus was central but could
382 . L. LiiTZEN and H . UEBERBERG
•
Fig. 5. Different degrees of tumour-like profileration of the L. c. HE-staining, X 2-7.
just as often be peripheral. The honeycomb-like cells were rich in lipoids. They resembled the cells of the adrenal cortex (Fig. 6). In the nodes containing densely packed eosinophile cells, there was hardly any lipoid material. There were further characteristic findings in the tumours which were in an advanced stage of growth. Capillarisation occurred. Wide, distended bloodfilled cavities could be seen which were also the beginnings of hemorrhages. In isolated central sections liquefaction was visible. Small cavity formations alternated with cyst-like clusters. Some were filled with protein-containing material or erythrocytes. We have interpreted these as being disintegrated tubules. Although there was no doubt about the extensive growth of these tumours, in no case did we observe a true invasive growth into the tubules. We think it is more likely that the tumour tissue grew around the tubules and thus lead to a degeneration of the germinal epithelium. No protrusion into the capsule of the testis could be proved. Almost without exception the tumours gave the impression that they were sharply compact, but were not bound by a true capsule. In the interior delicate collagenous threads were produced. The testicular tissue which was surrounded by the nodes was often
Testes of Old Albino Rats' 383
Fig. 6. Lipoid in the L. c. tumours. Sudan black-staining, X I40.
clearly seen to be compressed. It should be particularly mentioned that we often saw mitoses in the well-advanced tumours. The cytological picture after the pigment reaction showed a yellowishbrown colour which was most distinct after the argentaffine reaction. The lipofuscine reaction was only weakly positive. In connection with the hemorrhages there was a great deal of iron-positive material available. In cases where there was extensive spread of the tumour the remaining testicular parenchyma was atrophic. Calcification was seen in a few cases.
Discussion According to our experience atrophy of the tubules in the testes of the rat can be found to the same extent in young animals, that is to say in the age group up to I year. The giant cells which occur in many cases are macrophages which have wandered from the interstices into the tubules. Other giant cells emanate from spermatogonia as a result of defects in the division processes. JAFFE and v. GAVALLER (I958) have already referred to such occurrences.
384' L.
LUTZEN
and H.
UEBERBERG
A more difficult question to answer is whether the proliferation of the L. c. is a characteristic of a true growth. Here one has to differentiate between stringlike proliferations and nodular and adenomatous formations. In principle, there is no difference between both forms even if the former never extend beyond a certain size. The nodular or adenomatous formations which in some cases affect entire testis, stem from the microscopically small nodular proliferations of the L. c. Apparently primary pituitary influences are of importance in the formation of the L. c. tumours, but we are not aware of their basic principles. Analogous to man the testosterone production of the aging testis could be reduced and, therefore, through a feedback mechanism stimulate the increase in ICSH. We are also in the dark as to whether the adenomata would disappear or atrophy after removal of the pituitary.
It is certain that the majority of comparable nodular hyperplasias of endocrine organs are not autonomous growth processes; the same is true for prostatic and mammary adenomata and myomata of the uterus. It is known in man that the L. c. tumours are hormonally active. Should they appear in childhood, they lead to a clinical form of pubertas praecox (KAUFMANN, 1966). In adults the L. c. adenoma produces increased androgens in the same way; however, except for a possible gynecomastia, hormonal effects are absent. At the moment we hesitate to speculate whether they are hormonally active in the rat. The tumours which we observed had developed in testes which were previously intact. This we know as the animals when younger had been used successfully for breeding purposes. Damage to the germinal epithelium which could lead to L. c. hyperplasia as for instance in the case of cryptorchism, pseudohermaphroditism or testicular atrophy (PALLASKE, 1931; INNES, 1942) does not come into question as being causal in our experimental material. Taking as a basis the fact that pituitary factors playa role in the origin of the L. c. adenoma, then the question is still open whether and when autonomous growth results from the growth controlled by the pituitary. A genuine tumour growth in the L. c. can be assumed in the large adenomata which occupy the entire testis. The evidence of mitotic activity also confirms this. Experimental investigations on old male rats (removal of the pituitary, testis transplantation) would clarify this question and such experiments are planned.
L. c. adenomata demonstrated here in old rats have never been found by us in young animals. Other types of testicular tumours were not found in the present series.
Testes of Old Albino Rats' 385
Zusammenfassung Wir untersuchten die Hoden von 90 mannlichen Albino-Ratten, die ein Lebensalter von 2 Jahren hatten. Bei 27 Tieren wurden strangformige Hyperplasien der Leydigschen Zwischenzellen festgestellt. 49 Tiere wiesen knotigc oder adenomatose Proliferationen in einem oder beiden Hoden auf. Die GroGe war unterschiedlich. Neben solchen, die mikroskopisch klein waren und jenen, die den ganzen Hoden betrafen, kamen aile Groll en vor. Wir bezeichneten sie als Adenome der Leydigschen Zwischenzellen. Bosartiges Wachs tum wurde nidlt gefunden. Bei einem Lebensalter von Tiercn bis z u I Jahr treten diese Veranderungen nach unserer ErfahruJ\g nicht auf. Ober die Entstehung dieser Adenome JaGt sich nichts Endgiiltiges sagen. Jedoch mochten wir ann ehmen, daG es sich urn hypophysar ausgeloste Prozesse handelt, die dann schlieGlich in ein autonomes Wachstum iibergehen konnen. AuGer den geschwulstmaGigcn Veranderungen der Leydigschen Zwischenzell en waren atrophische Veranderungen des Keimepithels vorhanden, die aber in der gleichen Weise bei jiingeren Tieren vorkommen.
References BRAUN, H. : Virchows Arch. path. Anat. 304,106 (1939) CRAIN, R.: Amer.]. Path. 34,JII (1958) INNES, ].R.M.:]' Path. Bact. 54,485 (1942) JAFFE, R. and GAVALLER, B. v.: Mannliche Genitalorgane. In : Pathologie der Laboratoriumstiere; hrsg. von COHRS, JAFFE und MEESSEN, 1. Bd., Springer-Verlag, Berlin (1958) KAUFMANN, J. : Der Urologe 2, 84 (1966) KRUTSAY, M.: Zbl. allg. Path. path. Anat. II4, 374 (1971) KUNZE, A. : Virchows Arch. path. Anat. 204, 144 (1922) PALLASKE, G.: Virchows Arch. path. Anat. 281, 856 (1931) RATCLIFFE, H. 1. : Amer. ]. Path. 16,237 (1940) SCHARDEIN, J. 1., FITZGERALD,]. E., and KAUMP, D.H.: Path. Vet. 5, 238 (1968) SCHLEGEL, M. : 1924 cit. INNES (1942) SCHLOTTHAUER, C. F., McDONALD, J. R ., and BOLLMAN, J. 1.: Der Urologe 40,539 (1938) SCULLY, R. E. and COFFIN, D. 1. : Cancer 5, 592 (1952) Dr. 1. LUTZEN, Prof. Dr. H. UEBERBERG, Abt. f. expo Pathologie, Fa. Dr. K. Thomae GmbH, D-795 BiberachJRill
A Study on Morphological Changes in the Testes of Old Albino Rats Untersuchungen tiber Hodenveranderungen bei alten Albinoratten LEHNHARD LUTZEN
and
HEINZ UEBERBERG
With 6 Figures· Received April 17, 1973 . Accepted May
II,
1973
Summary We studied the testes of 90, two year-old male albino rats. In 27 animals string-like hyperplasia of the Leydig cells were found. 49 animals showed nodular or adenomatous proliferation in one or both testes. The size varied ranging from microscopically detectable lesions to others which occupied th e entire testis. We refer to them as adenomata of the Leydi g cells. Malignant lesions were not found. In our experience the changes were not present in animals up to one year of age. No definite conclusions can be made as to the origin of these adenomata. At the moment, however, we would like to hypothesise that they a re due initially to a process induced by the pituitary and that afterwards their growth becomes autonomous. Apart from the tumour-like changes in the Leydig cells, atrophic changes in the germinal epithelium were also present, which, howeve r, appeared also in the young animals in the same form.
Many papers can be found in the literature dealing with changes-particularly tumour formation-in the testes of animals (SCHLEGEL, 1924). They seem mostly to concern the dog (KUNZE, 1922; SCHLOTTHAUER, 1938; BRAUN, 1939; INNES, 1942; SCULLY, 1952). It is surprising that virtually nothing has been published about the type and incidence of age-dependent changes in the testes of the albino rat and in particular nothing about tumours, although this species is the one most commonly used in experimental work. Presumably the reason is that animal experiments are normally carried out over a short period of time and mainly with younger fully-grown animals. RATCLIFFE (1940) found 2 tumours of the testes amongst 231 spontaneous tumours in male rats which he designated fibrosarcoma. CRAIN (1958) on the other hand found interstitial adenomata of the testes in 35 out
378 . L. LUTZEN and H. UEBERBERG
of 334 male rats aged 18-24 months. In the work of SCHARDEIN, FITZGERALD and KAUMP (1968) due to the large number of animals used the occurrence of spontaneous tumours within a strain of rats is reported, but no mention is made of the testis. Our knowledge of age-dependent changes in the testis of the rat becomes more significant with the planning of long-term experiments, as for instance is done in the testing of chemical substances for carcinogenic properties. Such investigations are carried out over a period of up to 2 years. We had the opportunity of performing a morphological investigation on a large number of old rats which had never before been used for experimental purposes. In the following work we report on our findings concerning the testis.
Material and Methods The experiments were carried out on the testes of 90 male SPF-albino rats, strain FW 49/Biberach. The average weight and age of the animals were 650 g and 2 years (720-778 days) respectively. Five rats were housed together in an SPF all wire Type III cage under SPF-conditions. Temperature and humidity were kept constant by means of a complete airconditioning system (20 o+l o C, 55-60% humidity). Alternating 12 hour periods of light and dark were maintained in the animal house. During the periods of light the illumination intensity was 150 Lux. Food: Altromin R "fortified" (steam-sterilised) and water were available ad libitum. The animals were sacrificed under anaesthesia (Nembutal - 1 ml/kg = 50 mg/kg) by slitting the aorta. The testes were treated with BOUIN'S fixing solution. The organs were embedded in Paraplast and serial sections were cut which were stained as follows:-I. HE stain; 2. Sudan black stain; 3. v. Gieson stain; 4. v. Kossa stain; 5. Azan stain; 6. PAS reaction. To identify pigments the following reaction according to KRUTSAY (1971) was carried out; 1. treatment with ammoniacal alcohol to remove precipitates caused by formalin, staining with haematoxylin-eosin ; 2. Berlin-blue reaction; 3. Lipofuscin identification; 4. bleaching with KMn0 4 ; 5. Argentaffine reaction; 6. Ferri-ferricyanide-reaction. In order to identify any crystals the prepared slices were viewed under polarised light.
Results During the post-mortem examination of our test material we were struck by the difference in size of the testes. The average weight was 4.41 g. There was, however, a wide range of variability. For instance weights ranging from 1.51 - 13.53 g were recorded. 15 of the 90 animals showed a difference in weight between the left and right testis. The colour varied in accordance with the consistency. Soft, elastic testes were mainly light yellow. In some the surface was a yellowish-brown mottled colour, and they had a firm elastic consistency. Others had a variable consistency, in which the Tunica albuginea was transparent. The testis itself was filled with an amber-coloured
Testes of Old Albino Rats' 379
Fig.
1.
Loss of the germinal epithelium with the appearance of giant-cells. HE-staining, x 205.
liquid interspersed with white threads. In a few cases firm as well as soft areas were found in one and the same testis. Histological changes in the testis were observed in 76 of the 90 animals. No anomalies nor traumatic lesions nor the sequelae of these were seen. There were two main types of changes in our test material: degenerative or atrophic signs in the tubules, and hyperplastic or tumour-like growth of the Leydig cells (L. c.). In many cases just from the macroscopic picture, and from the weight and consistency of the testis, deviations from the norm could be predicted. In some cases only one testis was involved. Atrophy of tubules could be seen 24 times in the 90 animals. In nine instances the whole testis was affected, in other instances only isolated segments. Sometimes a complete failure of spermatogenesis ensued. Often the formation of giant-cells could be seen and all manner of cell shapes and sizes. Alongside cells with a large round hyperchromatic nucleus were to be found others which were not enlarged, or simply bizarre shapes with lobular nuclei (Fig. I). In the region of the atrophic tubules the L. c. had no special peculiarities. The interstitial tissue was sometimes strongly disintegrated and filled with oedematous fluid (Fig. 2).
380 •
Fig.
2.
1. UiTZEN and H.
UEBERBERG
Atrophy of the germinal epithelium with excessive interstitial oedema. HE-staining,
x I40.
Fig. 3. String-like hyperplasia of the 1. c., intact germinal epithelium. HE-staining, X 140.
Testes of Old Albino Rats' 38I
Fig. 4. "Miliary" profile ration of the L. c. HE-staining, X I40.
On the whole, however, the proliferation of L. c. which was found in 70 out of 90 cases was the most remarkable feature. In 27 cases the L. c. were spread out in the interstices in string-like shapes (Fig. 3). Therefore, our reference to a "string-like hyperplasia" of the L. c. Generally speaking they appeared as tightly packed, strongly eosinophile-tinged polygonal cells mostly with a central cell nucleus. Degenerative changes in the germinal epithelium were not seen in the region of these L. c. hyperplasia. Spermatogenesis was unaffected. Nodular profileration varying in degree and extent was apparent in 49 animals in 4 of which only one testis was affected. States ranging from microscopically small "miliary" foci (Fig. 4) to almost complets tumour-like change of a testis were found (Fig. 5). This figure also clearly shows the multiplicity of the growth in which a conglomeration of single nodes occurs. From the histological point of view, there was no difference in cell picture between the microscopically small L. c. nodes and the string-like hyperplasia. In contrast, the cytological picture in the large nodular proliferation showed partial differentiation in the cells. The cytoplasm was no longer as dense and did not have the strong eosinophile staining, but had a more honeycomb-like structure. Sometimes the cell nucleus was central but could
382 . L. LiiTZEN and H . UEBERBERG
•
Fig. 5. Different degrees of tumour-like profileration of the L. c. HE-staining, X 2-7.
just as often be peripheral. The honeycomb-like cells were rich in lipoids. They resembled the cells of the adrenal cortex (Fig. 6). In the nodes containing densely packed eosinophile cells, there was hardly any lipoid material. There were further characteristic findings in the tumours which were in an advanced stage of growth. Capillarisation occurred. Wide, distended bloodfilled cavities could be seen which were also the beginnings of hemorrhages. In isolated central sections liquefaction was visible. Small cavity formations alternated with cyst-like clusters. Some were filled with protein-containing material or erythrocytes. We have interpreted these as being disintegrated tubules. Although there was no doubt about the extensive growth of these tumours, in no case did we observe a true invasive growth into the tubules. We think it is more likely that the tumour tissue grew around the tubules and thus lead to a degeneration of the germinal epithelium. No protrusion into the capsule of the testis could be proved. Almost without exception the tumours gave the impression that they were sharply compact, but were not bound by a true capsule. In the interior delicate collagenous threads were produced. The testicular tissue which was surrounded by the nodes was often
Testes of Old Albino Rats' 383
Fig. 6. Lipoid in the L. c. tumours. Sudan black-staining, X I40.
clearly seen to be compressed. It should be particularly mentioned that we often saw mitoses in the well-advanced tumours. The cytological picture after the pigment reaction showed a yellowishbrown colour which was most distinct after the argentaffine reaction. The lipofuscine reaction was only weakly positive. In connection with the hemorrhages there was a great deal of iron-positive material available. In cases where there was extensive spread of the tumour the remaining testicular parenchyma was atrophic. Calcification was seen in a few cases.
Discussion According to our experience atrophy of the tubules in the testes of the rat can be found to the same extent in young animals, that is to say in the age group up to I year. The giant cells which occur in many cases are macrophages which have wandered from the interstices into the tubules. Other giant cells emanate from spermatogonia as a result of defects in the division processes. JAFFE and v. GAVALLER (I958) have already referred to such occurrences.
384' L.
LUTZEN
and H.
UEBERBERG
A more difficult question to answer is whether the proliferation of the L. c. is a characteristic of a true growth. Here one has to differentiate between stringlike proliferations and nodular and adenomatous formations. In principle, there is no difference between both forms even if the former never extend beyond a certain size. The nodular or adenomatous formations which in some cases affect entire testis, stem from the microscopically small nodular proliferations of the L. c. Apparently primary pituitary influences are of importance in the formation of the L. c. tumours, but we are not aware of their basic principles. Analogous to man the testosterone production of the aging testis could be reduced and, therefore, through a feedback mechanism stimulate the increase in ICSH. We are also in the dark as to whether the adenomata would disappear or atrophy after removal of the pituitary.
It is certain that the majority of comparable nodular hyperplasias of endocrine organs are not autonomous growth processes; the same is true for prostatic and mammary adenomata and myomata of the uterus. It is known in man that the L. c. tumours are hormonally active. Should they appear in childhood, they lead to a clinical form of pubertas praecox (KAUFMANN, 1966). In adults the L. c. adenoma produces increased androgens in the same way; however, except for a possible gynecomastia, hormonal effects are absent. At the moment we hesitate to speculate whether they are hormonally active in the rat. The tumours which we observed had developed in testes which were previously intact. This we know as the animals when younger had been used successfully for breeding purposes. Damage to the germinal epithelium which could lead to L. c. hyperplasia as for instance in the case of cryptorchism, pseudohermaphroditism or testicular atrophy (PALLASKE, 1931; INNES, 1942) does not come into question as being causal in our experimental material. Taking as a basis the fact that pituitary factors playa role in the origin of the L. c. adenoma, then the question is still open whether and when autonomous growth results from the growth controlled by the pituitary. A genuine tumour growth in the L. c. can be assumed in the large adenomata which occupy the entire testis. The evidence of mitotic activity also confirms this. Experimental investigations on old male rats (removal of the pituitary, testis transplantation) would clarify this question and such experiments are planned.
L. c. adenomata demonstrated here in old rats have never been found by us in young animals. Other types of testicular tumours were not found in the present series.
Testes of Old Albino Rats' 385
Zusammenfassung Wir untersuchten die Hoden von 90 mannlichen Albino-Ratten, die ein Lebensalter von 2 Jahren hatten. Bei 27 Tieren wurden strangformige Hyperplasien der Leydigschen Zwischenzellen festgestellt. 49 Tiere wiesen knotigc oder adenomatose Proliferationen in einem oder beiden Hoden auf. Die GroGe war unterschiedlich. Neben solchen, die mikroskopisch klein waren und jenen, die den ganzen Hoden betrafen, kamen aile Groll en vor. Wir bezeichneten sie als Adenome der Leydigschen Zwischenzellen. Bosartiges Wachs tum wurde nidlt gefunden. Bei einem Lebensalter von Tiercn bis z u I Jahr treten diese Veranderungen nach unserer ErfahruJ\g nicht auf. Ober die Entstehung dieser Adenome JaGt sich nichts Endgiiltiges sagen. Jedoch mochten wir ann ehmen, daG es sich urn hypophysar ausgeloste Prozesse handelt, die dann schlieGlich in ein autonomes Wachstum iibergehen konnen. AuGer den geschwulstmaGigcn Veranderungen der Leydigschen Zwischenzell en waren atrophische Veranderungen des Keimepithels vorhanden, die aber in der gleichen Weise bei jiingeren Tieren vorkommen.
References BRAUN, H. : Virchows Arch. path. Anat. 304,106 (1939) CRAIN, R.: Amer.]. Path. 34,JII (1958) INNES, ].R.M.:]' Path. Bact. 54,485 (1942) JAFFE, R. and GAVALLER, B. v.: Mannliche Genitalorgane. In : Pathologie der Laboratoriumstiere; hrsg. von COHRS, JAFFE und MEESSEN, 1. Bd., Springer-Verlag, Berlin (1958) KAUFMANN, J. : Der Urologe 2, 84 (1966) KRUTSAY, M.: Zbl. allg. Path. path. Anat. II4, 374 (1971) KUNZE, A. : Virchows Arch. path. Anat. 204, 144 (1922) PALLASKE, G.: Virchows Arch. path. Anat. 281, 856 (1931) RATCLIFFE, H. 1. : Amer. ]. Path. 16,237 (1940) SCHARDEIN, J. 1., FITZGERALD,]. E., and KAUMP, D.H.: Path. Vet. 5, 238 (1968) SCHLEGEL, M. : 1924 cit. INNES (1942) SCHLOTTHAUER, C. F., McDONALD, J. R ., and BOLLMAN, J. 1.: Der Urologe 40,539 (1938) SCULLY, R. E. and COFFIN, D. 1. : Cancer 5, 592 (1952) Dr. 1. LUTZEN, Prof. Dr. H. UEBERBERG, Abt. f. expo Pathologie, Fa. Dr. K. Thomae GmbH, D-795 BiberachJRill