Transcription factor GATA-2 contains two copies of a highly conserved zinc finger domain and plays unique roles at an early stage of hematopoietic differentiation. In the mouse pituitary gland, Pit-1-GATA-2 protein-protein interaction has been shown to lead to gene-specific actions to obtain cell-specific roles. In this study, we investigated the expression of GATA-2 and Pit-1 in human pituitary adenomas using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical techniques. By immunohistochemical analysis, GATA-2 was detected in all of the gonadotropinsubunit (Gn-su)-positive adenomas (n ؍ 8) and in four of five thyroid-stimulating hormone (TSH)-secreting adenomas, but its incidence was low in the other types of adenomas. Pit-1 protein was detected in 4 of 5 TSH-secreting adenomas and in 10 of 10 growth hormone (GH)-secreting adenomas. By RT-PCR analysis, GATA-2 was detected in all Gn-supositive adenomas and TSH-secreting adenomas, and Pit-1 was detected in all TSH-secreting adenomas and GH-secreting adenomas. These results suggested that GATA-2 contributes to the functional expression and the differentiation of Gn-su-positive adenomas and the TSH-secreting adenomas and that the interaction between GATA-2 and Pit-1 can lead to gene-specific action and differentiation of TSH-secreting adenomas. It is further speculated that GATA-2 and transcriptional interaction with Pit-1 play roles in the functional differentiation of specific pituitary adenomas.
p27 (Kip1) plays regulatory roles in the cell cycle by inhibiting the activity of cyclin dependent kinases (CDKs). This immunohistochemical study is aimed at elucidating the expression of p27 in human pituitary and in various types of pituitary adenomas in order to clarify its role in the regulation of proliferation. Sixteen normal pituitary glands and 179 human pituitary adenomas were used for immunohistochemical studies. The tissues were fixed in 10% formalin and embedded in paraffin. Indirect peroxidase method was performed after heat-induced antigen retrieval using a monoclonal antibody against p27 protein. p27 protein was expressed in the nuclei of all 16 normal human pituitary glands. p27 protein was also expressed in 128 of 179 cases of pituitary adenomas (71.5%). A marked decrease of p27 expression was noted in ACTH-secreting adenomas, 8/20 (40.0%), compared with other types of pituitary adenomas--GH-secreting adenomas, 35/46 (76.1%); PRL-secreting adenomas, 22/33 (66.7%); TSH-secreting adenomas, 8/11 (72.7%); and nonfunctioning adenomas, 55/69 (79.7%). These results suggest that p27 may play some role in the regulation of proliferation in all types of pituitary adenomas. The lower levels of p27 in ACTH-secreting adenoma is of particular interest with respect to the intermediate lobe-derived pituitary tumor developed in p27 knockout mice.
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