| Project/Area Number |
04454183
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Tokai University |
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Principal Investigator |
OSAMURA Yoshiyuki Tokai University, School of Medicine, Professor, 医学部, 教授 (10100992)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEKOSHI S Same as above assistant Professor, 医学部, 助手 (70216878)
佐藤 慎吉 東海大学, 医学部, 講師 (80119677)
堤 寛 東海大学, 医学部, 助教授 (80138643)
TSUTSUMI Y Same as above associated Professor
SATO S Same as above instructor
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Pituitary gland / adenoma / growth hormone / prolactin / TSH / Pit-1 / Transgenic animal / Immunohistochemistry / 転写促進因子 / 下垂体腺腫過形成 / factor growth hormone releasing(GRF) / pit-1遺伝子 / 成長ホルモン / アクロメガリー / プロラクチン / 甲状腺刺激ホルモン |
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| Research Abstract |
It has been reported that the pituitary-specific transcriptional factor (Pit-1/GHF-1) gene produces nuclear binding protein composed of 291 amino acids (1). Semmons and colleagues (3) recently reportedthat in developing rat pituitary glands, Pit-1mRNA is distributed in all anterior cells, but that Pit-1 protein is expressed in certain cells (i.e., GH,PRL,TSH cells).
PRODUCTION OF ANTI-HUMAN (h) Pit-1 ANTIBODY AND IMMUNOHISTOCHEMISTRY
A 14 amino acid peptide KVRRIKLGYTQTNV was produced on a peptide synthesizer corresponding to the huamn Pit-1 amino acid sequence 149-162. Polyclonal antibody was raised againt the synthetic peptide in rabbits. The immunohisotchemical studies showed that many cells in the normal pituitary glands obtained at autopsy were positive for Pit-1 protein which was strictly localized in the nuclei. In serial sections, Pit-1 product was frequently localized in the nuclei of GH cells, PRL cells and somatomammotrophs (GH+PRL) (Fig.). The double staining method revealed
… More
that Pit-1 protein was localized in the nuclei of GH cells and PRL cells. These results may suggest the role of Pit-1 product in functional differentiation and maintenance of pituitary cells toward GH and PRL in physiologic condition.
IMMUNOHISTOCHEMICAL DETECTION OF hPit-1 PROTEIN IN THE HUMAN PITUITARY ADENOMAS
Among 86 patients studied immunohistochemically, a total of 38 adenomas were positive for Pit-1 product. In these 38 adenomas, Pit-1 product was specifically localized in the nuclei. All TSH ade-nomas were positive for Pit-1 product. 27 of 51 GH producing adenomas were positive.
IMMUNOHISTOCHEMICAL DETECTION OF Pit-1 PROTEIN IN THE PITUITARY ADENOMAS OF hGRF TRANGENIC MICE
It has been well documented that human GRF transgenic mice can develop pituitary hyperplasia andadnomas after about 10 months. The adenomas are well demarcated and are composed of larger and morechromophobic monotonous cells comparing to those acidophilic cells in the hyperplastic areas. The adnoma cells are immunohistochemically positive for GH,PRL and hGRF.alpha subunit, LHbeta, FSHbeta and ACTH are negative. Scattered and hypertrophic TSHbeta positive cells are also present in the adenomas. The presence of hypertrophic TSHbeta positive cells are considered to be a marker of the neoplastic transformation of hyperplastic cells. The adenomas are more prominently positive for Pit-1 protein in the nuclei comparing to the staining in the hyperplastic areas. These results suggest that Pit-1 protein may play a role in the functional differentiation in adenomatous cells in addition to the autocrine stimulation via GRF production. Less
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