Expression of thyrotropin-releasing hormone messenger RNA in human pituitary adenomas with follicle-stimulating...

To assess the correlation between thyrotropin-releasing hormone (TRH) messenger RNA (mRNA) and the immunoreactive type of human pituitary adenomas.

Twenty-eight patients (14 to 73 years old) who had pituitary adenomas (18 nonfunctioning adenomas, 8 growth hormone-secreting adenomas, and 2 prolactinomas) underwent surgical treatment. Pituitaries removed at autopsy from four patients without evidence of pituitary disease were used as controls. Fragments of pituitary adenomas were processed for TRH mRNA by in situ hybridization (radioactive and nonradioactive) and for TRH peptide and anterior pituitary hormones (b-thyrotropin, b-follicle-stimulating hormone [FSH], bluteinizing hormone [LH], prolactin, and growth hormone) by immunohistochemistry with use of the avidinbiotin technique. Quantitative immunohistochemical studies were performed by using image analysis software. The signal was considered positive when more than 5% of the cells were stained.

Cells expressing TRH mRNA were detected in 22 of 28 pituitary adenomas--15 of 18 nonfunctioning pituitary adenomas, 5 of 8 growth hormone-secreting adenomas, and both prolactinomas. TRH peptide was revealed in only 10 adenomas, all expressing TRH mRNA as well. All but one nonfunctioning adenoma expressing TRH mRNA in more than 5% of the cells were b-FSH immunoreactive (15 of 16 cases; P<0.005, c 2 test), whereas only 6 of 16 nonfunctioning adenomas exhibited both b-thyrotropin and TRH mRNA and only 5 of 16 were positive for both b-LH and TRH mRNA.

These results confirm previous data demonstrating the presence of TRH mRNA and TRH peptide in human pituitary tumor cells. We further showed that the presence of TRH mRNA is significantly correlated with FSH immunoreactive gonadotropinomas. The release of FSH after an intravenous TRH test only in gonadotropinomas, together with local production of TRH, suggests a role for TRH in pathogenesis.