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

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

Animal model bearing pituitary prolactin-secreting adenomas (prolactinoma) induced by 17-β-estradiol (E₂) in both eutopic pituitary and ectopic pituitary grafted under the renal capsule was generated. Northern blotting assay indicated that PRL mRNA level in eutopic prolactinomas was higher than that in normal pituitaries and ectopic prolactinomas (P < 0.05-0.01). By polymerase 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 prolactinomas. No base change was detected in ectopic prolactinomas. Fusion gene transfection assayin vitro exhibited increased activity of the mutant promoter derived from eutopic prolactinoma (P < 0.01). These data suggested that the base change in the proximal promoter of rPRL gene may be associated with hyperexpression of rPRL gene in eutopic prolactinomas. The pathogenesis of eutopic and ectopic prolactinomas induced by E₂ in SD rats may be separate.