Estrogen (E2), acting via its nuclear receptors, has been implicated in tumor development and growth, particularly in the pathogenesis of breast cancer. E2 also modulates anterior pituitary hormone production and is a potent cell mitogen. Until recently, the actions of E2 were thought to be mediated by a single estrogen receptor (ER) isoform (ER alpha), and currently little is known of the pathophysiological relevance of the ER beta isoform. The presence of ER beta mRNA has been demonstrated by RT-PCR in the normal human pituitary, although expression of ER beta mRNA in human pituitary tumors has now been described. We have used semiquantitative RT-PCR to determine the relative levels of expression of ER beta mRNA in normal human pituitaries, non-functioning pituitary adenomas and GH-secreting tumors. ER beta mRNA was detected in normal pituitaries and all pituitary tumors examined. The ratio of ER beta mRNA to beta-actin mRNA expression was significantly reduced in non-functioning pituitary tumors (NFTs; 0.92 +/- 0.09; mean +/- SE; n = 23) compared with findings in normal pituitaries (1.56 +/- 0.21; mean +/- SE; n = 5; p < 0.05 Student's t-test). Studies of ER beta protein expression are required to determine the functional significance of reduced ER beta mRNA expression in NFTs.