PITUITARY CORTICOTROPH HYPERPLASIA IN RATS IMPLANTED WITH A MEDULLARY-THYROID CARCINOMA CELL-LINE TRANSFECTED WITH A CORTICOTROPIN-RELEASING HORMONE COMPLEMENTARY DEOXYRIBONUCLEIC-ACID EXPRESSION VECTOR

被引:25
|
作者
ASA, SL
KOVACS, K
HAMMER, GD
LIU, B
ROOS, BA
LOW, MJ
机构
[1] VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MIAMI,FL 33125
[2] UNIV MIAMI,DEPT MED,MIAMI,FL 33101
[3] UNIV MIAMI,DEPT NEUROL,MIAMI,FL 33101
[4] OREGON HLTH SCI UNIV,VOLLUM INST ADV BIOMED RES,PORTLAND,OR 97201
关键词
D O I
10.1210/en.131.2.715
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
CRH stimulates both the synthesis and release of ACTH and other derivatives of POMC by the adenohypophysis. It is uncertain, however, whether it also causes proliferation of corticotrophs. Patients with CRH-producing tumors develop Cushing's syndrome, and some have been reported to have pituitary corticotroph hyperplasia. We now report an animal model that accurately reproduces the human disorder of ectopic production of CRH by a neoplasm. Prolonged CRH secretion by a transplanted medullary thyroid carcinoma cell line stably transfected with a CRH cDNA under transcriptional control of a cytomegalovirus promoter resulted in corticotroph hyperplasia and hypertrophy; the percentage of ACTH-containing cells in animals bearing W2CRH tumors was increased at 9.8 +/- 0.5% (controls, 6.2 +/- 0.3%; W2 implanted tumors, 7.7 +/- 0.4%). Occasional mitotic figures were identified, and the cells were larger, with abundant cytoplasm but generally less intense immunohistochemical staining for ACTH due to relative degranulation compared to controls. Melanotrophs of the intermediate lobe were also increased in number and were larger, with abundant cytoplasm. No corticotroph adenomas were found. Our experiment accurately reproduces the gradually increasing CRH levels in the general circulation produced by a growing tumor, as found in the human ectopic CRH syndrome, and confirms that long term exposure to CRH excess, as produced by a tumor, results in an increased number of corticotrophs in the adenohypophysis.
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页码:715 / 720
页数:6
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