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教員個人(研究室)ページ

生体機構学研究室

担当教員 : 針谷 敏夫教授
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<研究略歴>

1975年東京大学農学部卒業、1980年東京大学大学院農学研究科博士課程修了。
農学博士。
京都大学医学部助手、講師を経て、 1990年より明治大学農学部講師、助教授、教授。
1986~88年米国カリフォルニア大学サンタクルツ校客員研究員。
専門研究分野は、応用動物科学、内分泌学、生体機構学。
近年は、プロラクチンというホルモンに関する研究を続けている。

<主な担当科目>

生体機構学Ⅰ・Ⅱ

data base

研究室 : 第一校舎5号館4階401号室

研究テーマ

生体機構学は体の構造とその機能との関係を理解することを目的とし、従来の解剖学の延長線上の学問ですが、 近年の科学技術の進歩とともに生体内の細胞の構造が解明されるにつれ、細胞学や分子生物学の分野とより 密接な関係を持ってきています。生体の構造や生命の維持に関わる情報はすべて、受精時に両親から伝えられた 遺伝子の中に含まれています。ところが細胞分裂時に情報はコピーされてそれぞれ伝えられ、すべての細胞が 同じ遺伝子を持っているにもかかわらず、細胞によりその情報の使い方が異なっています。 つまり、増殖・分化した個々の細胞において各遺伝子のスイッチのオン・オフが異なるため、発現に違いがでるのですがその機構はまだほとんど明らかになっていません。 生体内の遺伝子すべてにその発現をコントロールする機構が存在すると考えられ、すべての細胞や組織においてそれぞれが調和して機能することにより生命が正しく維持されています。 当研究室ではこのような遺伝子の発現機構の中で特にホルモンや成長因子遺伝子の発現調節に焦点を絞り研究を行っています。 当研究室では、プロラクチン(prolactin: PRL)というホルモンについて研究をしています。 プロラクチンは主に脳下垂体前葉で合成・分泌されるペプチドホルモンであり、その主な生理作用は哺乳類のメスにおける乳腺発達と乳汁分泌です(その他、両生類の変態調節などの多くの作用を持ちます)。 しかし近年、乳腺、精巣、胸腺、脾臓、子宮など下垂体以外の組織でも合成・分泌される異所性プロラクチンの存在が報告され、またリン酸化されたもの、糖付加されたもの、プロテアーゼ切断されたものなど多くの異型プロラクチンが存在することも報告されています。 そこで、当研究室では異所性プロラクチン、異型プロラクチンについて、その構造や機能、発現、分布の解析を行っています。 ・乳腺プロラクチンの解析 ・周産期心筋症とプロラクチン間の関連性の解析

研究室メンバー

博士後期;1名 博士前期2年 1名; 博士前期1年 1名; 学部4年 9名; 学部3年 7名

研究業績

<論文>

1.Harigaya.T, Sakai.S and Kohmoto.K. Induction of mammary prolactin receptors and lactose synthesis after ovariectomy in the pregnant mouse. Endocrinol. Japon. 25(2); 157-161, 1978.

2.Harigaya.T, Kohmoto.K, Ota.K and Yokoyama.A. Specific binding of prolactin to the mammary gland and lactose synthesis in pregnant rats after removal of ovaries or ovaries and adrenals. Endocrinol. Japon. 27(1); 39-41, 1980.

3.Sung.Y-Y, Kohmoto.K and Harigaya.T. Inhibition of prolactin receptors of mammary gland by antibiotics in ovariectomized pregnant mice. J. Chin. Soc. Anim. Sci. 10(1-2); 17-24, 1981.

4.Harigaya.T and Hoshino.K. Immunohistochemical localization of glucagon-like substance in the submandibular gland. Symposium for the Salivary Gland. 22; 35-37, 1981.

5.Harigaya.T, Sakai.S, Kohmoto.K and Shoda.Y. Influence of glucocorticoids on mammary prolactin receptors in pregnant mice after ovariectomy. J. Endocrinol. 94; 149-155, 1982.

6.Harigaya.T, Kohmoto.K and Hoshino.K. Immunohistochemical identification of prolactin-producing cells in the mouse adenohypophysis. Acta Histochem. Cytochem. 16; 51-58, 1983.

7.野々村光生、針谷敏夫、吉田修、星野一正 雄マウスにおける高プロラクチン血症の影響。 医学のあゆみ 125; 851-853, 1983.

8.Harigaya.T, Sakai.S, Kohmoto.K and Shoda.Y. Effects of cycloheximide in vitro on prolactin receptors in mouse mammary glands. Jpn. J. Zootech. Sci. 55; 858-863, 1984.

9.Harigaya.T and Hoshino.K. Immunohistochemical study of postnatal development of prolactin-producing cells in C57BL mice. Acta Histochem. Cytochem. 18; 343-351, 1985.

10.Nonomura.M, Hoshino.K, Harigaya.T, Hashimoto.H and Yoshida.O. Effects of hyperprolactinemia upon reproductions in male mice. J. Endocrinol. 107; 71-76, 1985.

11.Hashimoto.H, Yasuhara.T, Nakajima.T, Harigaya.T and Hoshino.K. Sexual dimorphism in amino acid compositions of mouse prolactin. Biochem. Biophys. Res. Commun. 130; 1209-1216, 1985.

12.Harigaya.T, Hashimoto.H and Hoshino.K. Effects of estrogen on prolactin cells in male mice. In: Pars Distalis of the Pituitary Gland – Structure, Function and Regulation, Edt by F. Yoshimura and A. Gorbman, Elsevier Science Publishers B.V., Amsterdam; pp.147-149, 1986.

13.Harigaya.T, Nakayama.K, Ohkubo, H, Nakanishi.S, Seo.H and Hoshino.K. Cloning and sequence analysis of cDNA for mouse prolactin. Biochim. Biophys. Acta. 868; 30-38, 1986.

14.Harigaya, T., Smith, W. C., and Talamantes, F. Hepatic placental lactogen receptors during pregnancy in the mouse. Endocrinology. 122; 1366-1372, 1988.

15.Harigaya.T, Smith.W.C and Talamantes.F. Comparison of placental lactogen-II and prolactin binding to liver membranes in pregnant mice. In: Prolactin gene family and its receptors – molecular biology to clinical problems, edt by K. Hoshino, Elsevier Science Publishers B.V., Amsterdam; pp107-114, 1988.

16.Mori.C, Harigaya.T, Hoshino.K and Fukuda.A. Effects of mouse prolactin on acrosomal reaction of spermatozoa in mice in vitro. In: Prolactin gene family and its receptors – molecular biology to clinical problems, edt by K. Hoshino, Elsevier Science Publishers B.V., Amsterdam; pp183-186, 1988.

17.Harigaya.T and Hoshino.K. Immunohistochemical identification of prolactin-producing cells in pituitary isografts in CBA mice. Anatomisher Anzeiger. 167; 205-212, 1988.

18.Mori.C, Hashimoto.H, Harigaya.T and Hoshino.K. Biological effects of prolactin on spermatozoa. J. Fertil. Implant. (Tokyo) 6; 75-78, 1989. 19.Harigaya.T. Effects of ovariectomy and administration of sex hormones on prolactin cell types in mice. Anim. Sci. Technol. (Jpn.) 62(8); 711-713, 1991.

20.針谷敏夫 マウス肝臓可溶化膜分画における胎盤性ラクトゲンIIの結合能 明治大学農学部研究報告 90; 7-12, 1991.

21.Harigaya.T. The important role of the adrenal gland on increases in the lactose content and the RNA/DNA ratio in the mouse mammary gland at ovariectomy-induced lactogenesis. Bull. Fac. Agr. Meiji Univ. 91; 17-22, 1991.

22.Yamamoto.M, Harigaya.T, Ichikawa.T, Hoshino.K, Nakashima.K. Recombinant mouse prolactin: Expression in Escherichia coli, purification and biological activity. J. Mol. Endocrinol. 8; 165-172, 1992.

23.Singtripop.T, Mori.T, Park.M-K, Shiraishi.K, Harigaya.T and Kawashima.S. Prolactin binding sites in normal uterus and the uterus with adenomyosis in mice. Zoological Science. 10; 353-360, 1993.

24.針谷敏夫、笹治春奈、飛弾大輔 妊娠マウスにおける下垂体中プロラクチンの免疫組織化学的検索 明治大学農学部研究報告 97; 95-102, 1993

25.Harigaya.T, Kitabayashi.N, Yoshikawa.K and Yamamoto.M. An enzyme immunoassay for the determination of serum prolactin in mice: developed by recombinant mouse prolactin. Anim. Sci. Technol. 65; 42-44, 1994.

26.Sakai.S, Mizuno.M, Harigaya.T, Yamamoto.K, Mori.T, Coffey.R..J and Nagasawa.H. Cause of failure of lactation in mouse mammary tumor virus/human transforming growth factor a transgenic mice. Proc. Soc. Exp. Biol. Med. 205; 236-242, 1994.

27.Mizuno.M, Yamamoto.K, Sakamoto.S, Mori.T, Harigaya.T, Matsubara.M, Coffey.R.J and Nagasawa.H. Normal and neoplastic mammary gland growth in MMTV/TGFa transgenic mice. In Vivo 8; 263-270, 1994.

28.Harigaya.T, Tsunoda.S, Mizuno.M and Nagasawa.H. Different gene expression of mouse transforming growth factor a between pregnant mammary glands and mammary tumors in C3H/He mice. Zoological Science. 11; 625-627, 1994

29.Harigaya.T, Yokoyama.H, Tsunoda.S and Nagasawa.H. Immunohistochemical localization of transforming growth factor a in mouse mammary glands and mammary tumors. Acta Histochem. Cytochem. 27; 279-282, 1994.

30.Harigaya.T, Tsunoda.S, Yokoyama.H, Yamamoto.K and Nagasawa.H. Mouse TGFa gene expression in normal and neoplastic mammary glands and uteri of four strains of mice with different potentials for mammary gland growth and uterine adenomyosis. Zoological Science. 11; 841-846, 1994.

31.Mizuno.M, Harigaya.T and Nagasawa.H. Human and mouse TGFa (hTGFa and mTGFa) and mammary gland growth in relation to hormones. Proceedings of the XVI International Cancer Congress, Edts Rao RS, Deo MG, Sanghvi LD, Monduzzi Editore; pp627-631. 1995.

32.Mizuno.M, Harigaya.T and Nagasawa.H. Hormonal Modulation of human and mouse TGFa expression in the mammary glands of MMTV/human TGFa transgenic virgin mice. Bull. Fac. Agr. Meiji Univ; 105; 1-6, 1995.

33.Harigaya.T, Imata.E and Mori.Y. Prolactin gene expression in mouse mammary glands during late pregnancy and lactation. Anim. Sci. Technol. 67(4); 484-485, 1996.

34.Harigaya.T, Tsuchiya.Y, Tsunoda.S and Nagasawa.H. The Southern blot analysis of mouse TGFa gene expressions in normal and neoplastic mammary glands. Bull. Fac. Agr. Meiji Univ. 108; 13-19, 1996.

35.Nagasawa.H, Mizuno.M, Hasegawa.M and Harigaya.T. Variable expression of human transgenes in SHN mice. Laboratory Animals. 30; 127-131, 1996.

36.Harigaya.T, Ogawa.H, Tsunoda.S and Nagasawa.H. The mRNA expression of neurocan, a brain-specific chondroitin sulfate proteoglycan, in neoplastic mammary glands in mice. Zoological Science. 13(5); 665-668, 1996.

37.Harigaya.T, Komori.M, Kawakami.T, Watanabe.H and Abe.M. Expression of prolactin gene in mouse placenta during late pregnancy: detection of mRNA and its translation product. Endocrine J. 44(1); 155-161, 1997.

38.Ishida.M, Hasegawa.T, Harigaya.T, Ishida.N and Mukoyama.H. Molecular cloning and nucleotide sequence of the equine testicular 3b-HSD mRNA. In Advances in Comparative Endocrinology, edt by S. Kawashima and S Kikuyama, Monduzzi Editore; pp533-537, 1997.

39.Hasegawa.T, Ishida.M, Harigaya.T, Ishida.N and Mukoyama.H. Molecular cloning, nucleotide sequence and tissue distribution of equine testicular 3b-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase messenger ribonucleic acid. J. Equine Sci. 9; 45-52, 1998.

40.針谷敏夫、今井ひとみ マウスプロラクチン遺伝子一部断片のクローニングとエキソン/イントロン境界の決定 明治大学農学部研究報告 116; 1-7, 1998.

41.Hasegawa.T, Ishida.M, Harigaya.T, Sato.F, Ishida.N and Mukoyama.H. Linear SRY Transcript in Equine Testis. J. Vet Med. Sci. 61(1); 97-100, 1999.

42.塩野正義、針谷敏夫 マウス脳におけるニューロカン遺伝子の発現と局在 明治大学農学部研究報告 123; 1-14, 2000.

43.Nogami.H, Matsubara.M, Harigaya.T, Katayama.M and Kawamura.K. Retinoic acids and thyroid hormone act synergistically with dexamethasone to increase growth hormone-releasing hormone receptor mRNA expression. Endocrinology. 141; 4396-4401, 2000.

44.Matsubara.M, Harigaya.T and Nogami.H. Effects of diethylstilbestrol on the cytogenesis of prolactin cells in the pars distalis of the pituitary gland of the mouse. Cell Tissue Res. 306; 301-307, 2001.

45.Nogami.H, Hiraoka.Y, Matsubara.M, Nonobe.E, Harigaya.T, Katayama.M, Hemmi.N, Kobayashi.S, Mogi.K, Aiso.S, Kawamura.K and Hisano.S. A composite hormone response element regulates transcription of the rat growth hormone-releasing hormone receptor gene. Endocrinology. 143(4); 1318-1326; 2002.

46.Harigaya.T, Komori.M, Watanabe.H, Watanabe.S and Matsui.T. Prolactin gene expression in mouse pancreatic islet. Anim.Sci.J. 73; 29-34, 2002.

47.Koizumi.M, Horiguchi.K, Tomita.Y, Kato.Y and Harigaya.T. Prolactin Gene Expression in the Mouse Nipple and Mammary Gland. Journal of Reproduction and Development. 46(6); 465-472, 2003.

48.Ishida.M, Ono.K, Taguchi.S, Ohashi.S, Naito.J, Horiguchi.K and Harigaya.K. Cathepsin gene expression in the mouse placenta during the latter half of pregnancy. Journal of Reproduction and Development. 50; 515-523, 2004

49.Horiguchi.K, Yagi.S, Ono.K, Nishiura.Y, Tanaka.M, Harigaya.T. Prolactin gene expression in mouse spleen Helper T cells Journal of Endocrinology. 183; 639-646, 2004.

50.Horiguchi.K, Naito.J, Fujisawa.T, Ohashi.S, Ishida.M and Harigaya.T. Identification of prolactin synthesis at early differentiation stage of T cells in the thymus. Acta Histochemica et Cytochemica. 38; 283-287, 2005.

51.Ishida.M, Ohashi.S, kizaki.Y, Naito.J, Horiguchi.K and Harigaya.T. Expression profiling of mouse placental lactogen II and its correlative expression genes using a cDNA microarray analysis in the developmental mouse placenta. Journal of Reproduction and Development. 53(1); 69-76, 2007

52.堀口 幸太郎、針谷 敏夫 下垂体ホルモン・プロラクチンの多様性-異所性プロラクチンと異型性プロラクチン- 明治大学農学部研究報告 56-2; 41-49, 2006

53.Horiguchi.K, Naito.J, Ishida.M and Harigaya.T. The Effect of Estrogen on the Phosphorylation of Prolactin in the Mouse Pituitary Gland. Journal of Reproduction and Development. 53(3); 915-922. 2007

54.Horiguchi.K, Fukuta.S, Yoshida.M, Kosugi.T, Naito.J, Ishida.M, and Harigaya.T. Estrogen regulats the serum level of phosphorylated prolactin in mice. Journal of Reproduction and Development. 53 (4); 515-523. 2007

55.石田充代、針谷敏夫 雄生殖器におけるプロラクチンの機能 異所性および異型プロラクチンの観点からオスの生殖におけるPRLの機能を異所性および異型PRLを交えてまとめた。明治大学農学部研究報告 57 (4); 143-149. 2008

56.Ishida M, Yoshida M, Fukuta S, Uemura K, Iijima M, Horiguchi K and Harigaya T. Analysis of prolactin gene expression and cleaved prolactin variants in the mouse testis and spermatozoa. Journal of Reproduction and Development 56(6):567-574.2010.

57.Nakajima.R, Hirota.A, Suzuki.M, Ota.C, Kamiya.C, Ikeda.T, Ishida.M and Harigaya.T. Detection of Vasoinhibin and Cathepsin D in Pregnancy Induced Hypertension and Peripartum Cardiomyopathy Patiants. Journal of Japan Society for the Study of Hypertension in Pregnancy 19; 171-172. 2011

58.Ishida M, Maehara M, Watanabe T, Yanagisawa Y, Takata Y, Nakajima R, Suzuki M, Harigaya T. Vasoinhibins, N-terminal mouse prolactin fragments, participate in mammary gland involution.J Mol Endocrinol.279-87. 2014.

59.Nakajima R, Ishida M, Kamiya C, Yoshimatsu J, Suzuki M, Hirota A, Ikeda T, Harigaya T. Elevated vasoinhibin derived from prolactin and cathepsin D activities in sera of patients with preeclampsia. Hypertension Research 38, 899-901, 2015.

60. Nakajima R, Nakamura E and Harigaya T. Vasoinhibin, an N-terminal Prolactin Fragment, Directly Inhibits Cardiac Angiogenesis in Three-dimensional Heart Culture. Front. Endocrinol. 8(4). 2017

<著書・総説>

明解哺乳類の生理学[体液] (共著)学窓社、 ホルモンの分子生物学VOL.2 「成長ホルモン・プロラクチンファミリー」(共著)学会出版センター Pars Distalis of the Pituitary Gland-Structure,Function and Regulation(共著)Elsevier Science Publishers B.V Prolaction gene family and its receptors – molecular biology to clinical problems(共著)Elsevier Science Publishers B.V など

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