We used a nonisotopic in situ hybridization (ISH) method to investigate the expression of pituitary hormone, including glycoprotein hormone mRNAs in 17 somatotrophic and four lactotrophic adenomas. Our ISH studies of lactotrophic adenomas showed that their hormonal gene expression was confined to prolactin, whereas those of somatotrophic adenomas showed that some of them expressed plurihormonal genes. In some somatotrophic adenomas that were immunohistochemically negative for pituitary hormones, positive reactions, mainly for adrenocorticotropic hormone (ACTH), follicle-stimulating hormone beta subunit (FSH beta), and luteinizing hormone beta subunit (LH beta) mRNAs, were observed in our ISH studies. These results suggest that some somatotrophic adenomas may originate from plurihormonal primordial stem cells, which we have presumed serve as precursors for various hormone-expressing cells. It is unclear why some somatotrophic adenomas derived from plurihormonal primordial stem cells manifest clinically only as the acromegalic hyperfunction syndrome or gigantism. Additional translational factors or some other somatic mutations may play important roles in the clinical manifestations of such adenomas. In conclusion, some somatotrophic adenomas appear to be derived from plurihormonal primordial stem cells, whereas lactotrophic adenomas are well differentiated tumors that originate from lactotrophic cells, which represent the final stage of acidophilic cell line differentiation.