A point mutation of PRL gene in pituitary prolactin-secreting adenoma induced by 17-beta-estradiol in SD rats

Animal model bearing pituitary prolactin-secreting adenomas (prolactinoma) induced by 17-beta-estradiol (E-2) in both eutopic pituitary and ectopic pi tuitary grafted under the renal capsule was generated. Northern blotting as say indicated that PRL mRNA level in eutopic prolactinomas was higher than that in normal pituitaries and ectopic prolactinomas (P<0.05-0.01). By poly merase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, a point mutation from C to A occurring at -36 nt in proximal promoter of rat PRL (rPRL) gene was found only in eutopic pr olactinomas. No base change was detected in ectopic prolactinomas. Fusion g ene transfection assay in vitro exhibited increased activity of the mutant promoter derived from eutopic prolactinoma (P<0.01). These data suggested t hat the base change in the proximal promoter of rPRL gene may be associated with hyperexpression of rPRL gene in eutopic prolactinomas. The pathogenes is of eutopic and ectopic prolactinomas induced by Ep in SD rats may be sep arate.