IMMUNOHISTOCHEMICAL EXPRESSION OF PIT-1-PROTEIN IN PITUITARY-GLANDS OF HUMAN GRF TRANSGENIC MICE - ITS RELATIONSHIP WITH HORMONAL EXPRESSIONS

It has been suggested that pit-1 protein may play a role in the differ entiation of the anterior pituitary cells. The present immunohistochem ical studies were designed to elucidate the relationship between funct ional differentiation of pituitary adenoma and expression of pit-1 pro tein in human (h) GRF transgenic mice. Pituitaries from a 10 month old and a 6 month old transgenic mice were fixed in 4% paraformaldehyde a nd embedded in paraffin. The indirect immunoperoxidase method was perf ormed using antibodies against hGRF, GH, PRL, ACTH, alpha subunit (SU) , FSHbeta SU, LHbeta SU, TSHbeta SU, and pit-1 protein. Immunohistoche mical double staining was performed at light and electron microscopic levels. The pituitary glands of hGRF transgenic mice (both 10 month an d 6 month old) demonstrated diffuse hyperplasia of GH positive cells w ith coexpression of hGRF within the same cells. There were also scatte red cells which were positive for other hormones and hormone subunits in the hyperplastic pituitary. Three discrete nodules were found in th e pituitary gland of a 10 month old hGRF transgenic mouse and were ide ntified as adenomas. These adenomas were composed of enlarged round ce lls which were positive only for GH, hGRF, PRL and TSHbeta SU. Pit-1 p rotein was intensely expressed in the nuclei of the adenoma cells. The se results suggest the existence of an autocrine mechanism by hGRF in the formation of somato-lacto-thyrotroph adenoma via constitutive pit- 1 expression.