[Experimental investigation on the etiology and pathogenesis of pituitary prolactin-secreting tumor].
Male SD rats transplanted with an extra pituitary in the renal capsule and treated chronically with 17-beta-estradiol (E2) were used in the studies on the pathogenesis and the underlying mechanisms of pituitary prolactin-secreting tumor (prolactinoma). The results indicated that after long treatment with E2, prolactin-secreting tumor was generated in both eutopic and ectopic pituitary, accompanied by hyperprolactinemia and overexpression of PRL gene. No apparent difference was observed in histology and ultrastructure between them. Further investigations showed that some growth factors might be involved in the tumorigenesis of prolactinoma in vivo and in vitro. A point mutation was found in the proximal promoter of PRL gene only in eutopic prolactinoma by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), suggesting that the base change in the promoter may be related to the overexpression of PRL gene. This hypothesis has been confirmed by the increased activity of luciferase reporter fused to the mutant promoter in vitro. The coincidence of overexpression of PRL, TGF alpha and TGF beta 1 gene, and the point mutation detected in eutopic pituitary prolactinoma suggested that neuro-endocrine-immune interactions in vivo might be associated with pituitary prolactinoma formation. The mechanisms mediating tumorigenesis of eutopic and ectopic prolactinoma, respectively, may be different.
Wu
X M
XM
Department of Physiology, School of Basic Medicine, Peking Union Medical College & Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005.
D000818:Animals; D016228:Endothelial Growth Factors / Q000378:metabolism; D004958:Estradiol; D008297:Male; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000235:genetics; D017354:Point Mutation; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D015175:Prolactinoma / Q000209:etiology* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016228:Endothelial Growth Factors; D016212:Transforming Growth Factor beta; D004958:Estradiol; D011388:Prolactin