Expression of Corticotropin-Releasing Hormone Messenger Ribonucleic Acid in Human Pituitary Corticotroph Adenomas Associated with Proliferative Potential

Among the factors that promote the growth of human pituitary corticotroph adenomas (hPCAs), the proliferative potential of CRH secreted by hPCAs on these tumors is not well known. In this study, the CRH messenger ribonucleic acid (mRNA) transcripts were demonstrated on paraffin sections using the quantitative in situ hybridization method in 37 of 43 hPCAs, including 17 of 22 microadenomas, 15 of 15 macroadenomas, and 5 of 6 locally invasive adenomas according to Hardy's classification of pituitary adenomas. The more important findings were that CRH mRNA signal intensity in pituitary corticotroph adenoma cells was linearly correlated with Ki-67 tumor growth fractions (r = 0.802; P < 0.0001), and in macroadenoma and locally invasive adenoma cells it was significantly higher than in microadenoma cells (P = 0.035). On the other hand, CRH mRNA transcript accumulation was absent or negligible in 10 normal pituitary glands (P = 0.005). This is the first report of the frequent expression of CRH mRNA localized in human pituitary corticotroph adenoma cells. These results indicate that CRH from a local source of corticotroph adenoma cells not only has autocrine/paracrine functions in corticotroph adenomatous tissue, but also is an important factor associated with a proliferative potential of hPCAs.