Expression of human Pit-1 product in the human pituitary and pituitary adenomas. Immunohistochemical studies using an antibody against synthetic human Pit-1 product

Abstract

Objective: Pit-1, a member of a family of the POU-domain DNA binding factors, has been known as a pituitary-specific transcriptional factor that regulates functional differentiation toward somatotrophs, lactotrophs, and thyrotrophs in the rodent pituitary gland. The aim of this study is to elucidate the role of human Pit-1 (hPit-1) protein in the differentiation of human pituitary adenomas, using immunohistochemistry.

Design: Anti-human Pit-1 polyclonal antibody against synthetic peptide was applied to perform the avidin-biotinperoxidase complex method on paraffin sections of 75 surgically obtained pituitary adenomas and 12 nontumorous human pituitaries obtained at autopsy.

Results: In normal human pituitary glands, many cells were positive for hPit-1 product in the nuclei of somatotrophs, lactotrophs, and somatomammotrophs. Among 75 pituitary adenomas, hPit-1 product was expressed in 55 adenomas (73.3%). All (100%) of the growth hormone-positive and thyrotroph cell adenomas were positive for hPit-1 product. Unexpectedly, expression of hPit-1 was found in a limited number of adrenocorticotropic hormone-producing adenomas and clinically nonfunctioning adenomas, including gonadotroph cell adenomas, although localization was found only in occasional cells.

Conclusions: The invariable expression of hPit-1 protein in growth hormone-positive adenomas and thyroid-stimulating hormone-positive adenomas may suggest the role of Pit-1 protein in specific differentiation of the adenoma cells. The expression of hPit-1 in various other types of adenomas may indicate the involvement of other unidentified transcription factors or specific mediators that have roles in these differentiations. Our observation may provide some insight into the origin of cell types of some clinically nonfunctional adenomas.