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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 4 1414-1419
Copyright © 1999 by The Endocrine Society


Original Studies

Characterization of Prophet of Pit-1 Gene Expression in Normal Pituitary and Pituitary Adenomas in Humans1

Yoshio Nakamura, Takeshi Usui, Haruo Mizuta, Hiroyuki Murabe, Seiji Muro, Michio Suda, Kiyoshi Tanaka, Issei Tanaka, Akira Shimatsu and Kazuwa Nakao

Department of Medicine and Clinical Science (Y.N., T.U., H.Mi., H.Mu., S.M., M.S., K.T., I.T., K.N.), and Department of Laboratory Medicine (A.S.), Kyoto University Graduate School of Medicine, Kyoto 606-8397, Japan; and International Institute for Advanced Studies (T.U.), Kizugawa-dai Kizu-cho Soraku-gun Kyoto 619-0225, Japan

Address all correspondence and requests for reprints to: Dr. Takeshi Usui, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: tusui{at}kuhp.kyoto-u.ac.jp

Prophet of Pit-1 (Prop-1), which is a paired-like homeodomain transcription factor, is capable of binding to sites in an early enhancer of the Pit-1 gene and regulating its expression. According to a previous report, Prop-1 messenger RNA (mRNA) is expressed in the developing pituitary gland before Pit-1 mRNA expression and maximum expression are observed at e 12.0. After e 14.5, Prop-1 mRNA expression rapidly decreases, and only trace amounts of mRNA are detectable in adult mouse pituitary. Human Pit-1 is expressed considerably, not only in normal adult pituitary but also in pituitary adenomas, so we studied human Prop-1 gene expression in adult pituitary and pituitary adenomas. We also cloned human Prop-1 complementary DNA (cDNA) and sequenced the Prop-1 cDNAs in pituitary adenomas. The amino acid sequence of human Prop-1 cDNA that we cloned was identical to that of the previously reported sequence, except Thr substituted at codon 142 instead of Ala. This amino acid substitution is considered to be a polymorphism because it did not alter transcriptional activity, and 7 of 28 alleles were Ala. Human Prop-1 transcript was detected in normal adult pituitary, by Northern blot analysis, and in all pituitary adenomas examined by RT-PCR analysis. The expression of human Prop-1 in pituitary adenomas was confirmed by in situ hybridization in one of the somatotroph adenomas. The sequence analysis of human Prop-1 cDNAs in these pituitary adenomas revealed that there were no mutations, except 5 silent nucleic acid substitutions, suggesting that mutations of Prop-1 gene do not represent a frequent mechanism of human pituitary tumorigenesis.




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