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Effects of castration and testosterone treatment on male wistar rats's thymus development
128s
C-088 CCK/GLUCAGON EXPRESSION SELECTIVELY FOLLOWS AN ANORECTIC TUMOR PHENOTYPE FORMED FROM PLURIPOTENT TRANSFORMED ISLET CELLS. Madsen O.D., Rehfeld J., Holst J.J., Kofod H., Hansen B. and Lernmark A. Hagedorn Research Laboratory, Gentofte; University Hospital and Panum Institute, Copenhagen, Denmark. Monoclonal cultures of pluripotent rat islet tumor cells (MSL-cells) are highly heterogeneous and express several hormones including insulin, glucagon, somatostatin, and cholecystokinin (CCK). The purpose of this study was to investigate hormone expression from perifused tumor cells isolated from different tumor phenotypes formed by injecting MSL-clones in rats. MSL-G and its subclone, MSL-GZ, form hypoglycemic tumors and this phenotype has been maintained in a stable tumor-line, MSL-GZ-IN, by serial transplantation of the subclone. One rat carrying a MSL-G tumor became anorectic and hypoglycemic. By selective transplantation from this tumor it was possible to dissociate the two phenotypes leading to the establishment of a stable anorectic tumor-line, MSL-G-AN, with normoglycemia. Perifusion studies showed insulin to be the major product released from MSL-G;Z-IN, whereas both CCK and glucagon were secreted in large quantities from the MSL-G-AN. IBMX stimulated the release of both CCK and glucagon from MSL-G-AN Cells by Z-400%,but less than twice as much insulin was released by IBFlX from the MSL-GP-IN, whereas the secretin analogue, IOTyr-13Tyr_secretin, selectively stimulated hormone release from MSL-G-AN. The secretion rates (fmol/min/lOpl packed cells) following 0.1 mM IBMX stimulation were from MSL-G-AN cells: (glucagon; CCK; insulin) 350; 20; 0; compared to 0; 0; 200 in the MSLG2-IN cells. In conclusion, a clonal culture of MSL cells may express highly different phenotypes when grown in vivo. Tumors with anorectic phenotypes are characterized by high glucagon and CCK release while those with hypoglycemia release insulin. C-089 ~~~~~~~~~'S~SD~~ Carreira, Gabriela Conde, Ana Ccezho a& M. Deodata Institute I&&a Cabral, Listin, Portugal
EEFFKTSOF~TIONANDTES~ M. Teresa
Azevedo
I&mcar,
Chicdi, Calzolari , Cmsa and othersreferedthe relationbstveenthe sexualhormonesand thymusweight.Castrationseems to have an hypartrophic effecton thymus. Our studieswere done to verify if castration,done at differentrat's ages have the same influence on thymusdevelopmentand involution. Croupsof Wistarmale rats 3/4, 4/5, 6/7, 8/9, 12 and 14 weeks old were castratedunder ether anesthesiaand sacrifiedat 6/7, 7/8, 8/9, 12 and 22 weeks old. Other groupswere injectedwith 5 g of testosterone, daily,during 10 days and sacrifiedafter 4, 8 and 12 weeks. Histological studiesof thymusme done at differentages. Protein,nucleicacids and lipids contentsof the orgaq4weredetermine& 14 by thymusslilixoqxxationof (l- CIacetate,(U- Ctleucine,(2- CIthymineand (2-14C)uracil cues invitroarealsodecribed. The resultsseem to appointto a thyixolitic effectof testosterone when administeredin high doses. Castrationseems to affectonly the patternof thynt&s involution. Anotherhypothesisis that castrationhas an immediateeffecton lipidmetabolismwith emphasis on ketogenesis. Castrationseems to have a more delayedeffecton nucleicand proteinmetabolismof thymus. All these effectsdepamdon the age at which rats were castratedand also of the age of their death.
c-090 COMPARISOI! OF PEPTIDE
HORMOHES AND TPA AS TUMOR ?lARKERS IF! PATIEF!TS UITH BROACHOGEMIC CARCINOMA. Winkelmann, \‘I,, DeuR, ll., Allolio, 8., Kaulen, D., Schrappe-Bather, M. and Weidio. A. Inner~-~~edizin II der Univ. Koln, FRG Data on the incidence of ectopic hormones as tumor markers are frequently at variance. Therefore, we simultaneously measured dexamethasone-suppressed ACTH, HCG, ADH and tissue polypeptide antigen (TPA) in 296 patients calcitonin (Ct), with bronchogenic carc$noma (210 with small cell carcinoma, 130 with squamous 32 with adenocarcinoma and 24 with larqe cell carcinoma). In cell carcinoma. ACTH in-30 % of the patients small Fell carcinoma WV found non- suppressible elevated Ct in 23 % (193 - 16.X pg/ml), elevated X - SEM), (52.0 - 12.2 pg/ml HCG in 16 % (14.3 f 2.1 mIU/ml), elevated ADH in 34 % (10.1 - 1.7 pg/ml) and Squamous cell carcinoTa: ACTH 16 % (x = increpsed TPA in 34 % (325 2 42 U/L). HCG 16 % (11.2 - 1.5 mIU/ml), ADH 17.1 - 1.3 pg/ml), Ct 4 % (219 -+ 50 pg/mll, 23 % (7.2 2 0.3 pg/ml) and TPA 42 % (269 - 29 U/L). Adenocarcinoma: 13 %, 9 %, 9 %, 21 % and 56 X, respectively. Large cell carcinoma: 29 %, 13 %, 13 %, 33 % In patients with small cell carcinoma the simultaneous and 42 %. resoectivelv. measurement of ACTH, Et, HCG and ADH gives a high yield of positive results (74 X) indicating that this set of tumor markers is a promising aid in diagnoin patients with bronchogenic carcinoma sis and therapy control. In contrast, of other histological type TPA gives a higher yield of positive results than (Supported by Landesamt fiir Forschung MRW) peptide hormones.
C-088 CCK/GLUCAGON EXPRESSION SELECTIVELY FOLLOWS AN ANORECTIC TUMOR PHENOTYPE FORMED FROM PLURIPOTENT TRANSFORMED ISLET CELLS. Madsen O.D., Rehfeld J., Holst J.J., Kofod H., Hansen B. and Lernmark A. Hagedorn Research Laboratory, Gentofte; University Hospital and Panum Institute, Copenhagen, Denmark. Monoclonal cultures of pluripotent rat islet tumor cells (MSL-cells) are highly heterogeneous and express several hormones including insulin, glucagon, somatostatin, and cholecystokinin (CCK). The purpose of this study was to investigate hormone expression from perifused tumor cells isolated from different tumor phenotypes formed by injecting MSL-clones in rats. MSL-G and its subclone, MSL-GZ, form hypoglycemic tumors and this phenotype has been maintained in a stable tumor-line, MSL-GZ-IN, by serial transplantation of the subclone. One rat carrying a MSL-G tumor became anorectic and hypoglycemic. By selective transplantation from this tumor it was possible to dissociate the two phenotypes leading to the establishment of a stable anorectic tumor-line, MSL-G-AN, with normoglycemia. Perifusion studies showed insulin to be the major product released from MSL-G;Z-IN, whereas both CCK and glucagon were secreted in large quantities from the MSL-G-AN. IBMX stimulated the release of both CCK and glucagon from MSL-G-AN Cells by Z-400%,but less than twice as much insulin was released by IBFlX from the MSL-GP-IN, whereas the secretin analogue, IOTyr-13Tyr_secretin, selectively stimulated hormone release from MSL-G-AN. The secretion rates (fmol/min/lOpl packed cells) following 0.1 mM IBMX stimulation were from MSL-G-AN cells: (glucagon; CCK; insulin) 350; 20; 0; compared to 0; 0; 200 in the MSLG2-IN cells. In conclusion, a clonal culture of MSL cells may express highly different phenotypes when grown in vivo. Tumors with anorectic phenotypes are characterized by high glucagon and CCK release while those with hypoglycemia release insulin. C-089 ~~~~~~~~~'S~SD~~ Carreira, Gabriela Conde, Ana Ccezho a& M. Deodata Institute I&&a Cabral, Listin, Portugal
EEFFKTSOF~TIONANDTES~ M. Teresa
Azevedo
I&mcar,
Chicdi, Calzolari , Cmsa and othersreferedthe relationbstveenthe sexualhormonesand thymusweight.Castrationseems to have an hypartrophic effecton thymus. Our studieswere done to verify if castration,done at differentrat's ages have the same influence on thymusdevelopmentand involution. Croupsof Wistarmale rats 3/4, 4/5, 6/7, 8/9, 12 and 14 weeks old were castratedunder ether anesthesiaand sacrifiedat 6/7, 7/8, 8/9, 12 and 22 weeks old. Other groupswere injectedwith 5 g of testosterone, daily,during 10 days and sacrifiedafter 4, 8 and 12 weeks. Histological studiesof thymusme done at differentages. Protein,nucleicacids and lipids contentsof the orgaq4weredetermine& 14 by thymusslilixoqxxationof (l- CIacetate,(U- Ctleucine,(2- CIthymineand (2-14C)uracil cues invitroarealsodecribed. The resultsseem to appointto a thyixolitic effectof testosterone when administeredin high doses. Castrationseems to affectonly the patternof thynt&s involution. Anotherhypothesisis that castrationhas an immediateeffecton lipidmetabolismwith emphasis on ketogenesis. Castrationseems to have a more delayedeffecton nucleicand proteinmetabolismof thymus. All these effectsdepamdon the age at which rats were castratedand also of the age of their death.
c-090 COMPARISOI! OF PEPTIDE
HORMOHES AND TPA AS TUMOR ?lARKERS IF! PATIEF!TS UITH BROACHOGEMIC CARCINOMA. Winkelmann, \‘I,, DeuR, ll., Allolio, 8., Kaulen, D., Schrappe-Bather, M. and Weidio. A. Inner~-~~edizin II der Univ. Koln, FRG Data on the incidence of ectopic hormones as tumor markers are frequently at variance. Therefore, we simultaneously measured dexamethasone-suppressed ACTH, HCG, ADH and tissue polypeptide antigen (TPA) in 296 patients calcitonin (Ct), with bronchogenic carc$noma (210 with small cell carcinoma, 130 with squamous 32 with adenocarcinoma and 24 with larqe cell carcinoma). In cell carcinoma. ACTH in-30 % of the patients small Fell carcinoma WV found non- suppressible elevated Ct in 23 % (193 - 16.X pg/ml), elevated X - SEM), (52.0 - 12.2 pg/ml HCG in 16 % (14.3 f 2.1 mIU/ml), elevated ADH in 34 % (10.1 - 1.7 pg/ml) and Squamous cell carcinoTa: ACTH 16 % (x = increpsed TPA in 34 % (325 2 42 U/L). HCG 16 % (11.2 - 1.5 mIU/ml), ADH 17.1 - 1.3 pg/ml), Ct 4 % (219 -+ 50 pg/mll, 23 % (7.2 2 0.3 pg/ml) and TPA 42 % (269 - 29 U/L). Adenocarcinoma: 13 %, 9 %, 9 %, 21 % and 56 X, respectively. Large cell carcinoma: 29 %, 13 %, 13 %, 33 % In patients with small cell carcinoma the simultaneous and 42 %. resoectivelv. measurement of ACTH, Et, HCG and ADH gives a high yield of positive results (74 X) indicating that this set of tumor markers is a promising aid in diagnoin patients with bronchogenic carcinoma sis and therapy control. In contrast, of other histological type TPA gives a higher yield of positive results than (Supported by Landesamt fiir Forschung MRW) peptide hormones.