日本医科大学生理学第一講座1995年度業績目録
研究期間:1995年4月〜1996年3月
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研究概要
　性ステロイドの中枢作用についての神経内分泌学を中心に(1) 電気生理学, (2) 形 態学, (3) 行動学, (4) 分子生物学などの手法を用いて研究を進めている. 電気生理学では昨年から開始した無麻酔無拘束動物の自由行動下における内側視索前野 ニューロンの記録が軌道にのり, 雌ラット性行動の動機付けに関連する中枢活動の記録が行えるようになったのに加え, 下垂体細胞からのパッチクランプ記録が日常的に行われている. 免疫組織化学とin situ hybridizationを主な手技とする形態学グループはGnRHニューロンの個体発生におよぼす環境因子の影響をラットと硬骨魚で明らかにした. また, c-Fosタンパクの染色により雄ラットの性行動に関係する前脳部位の同定を試みている. 実験的脳梗塞による細胞脱落と学習機能の低下に対してエストロゲンが及ぼす効果を形態学的, 行動学的に評価し, 一定の改善が得られることを確認した. 性行動の調節機構では, 雌では腹側前乳頭体核の役割に注目し, 雄では非接触性勃起の調節回路の同定に取り組んでいる. 分子生物学的技術により, 従来から当教室の主要な研究課題の一つであったヒトグロビン遺伝子発現の制御機構と類似の調節がエストロゲン受容体遺伝子の調節にも存在することを示す所見を得ている. 今後, Differential Cloning法なども導入し, エストロゲンによるゲノムDNAの修飾の可能性を調べたい. また, 分子生物学, 行動学, 電気生理学の組み合わせにより, 膜レベルでのエストロゲン作用機構についての研究がスタートすることになっている.

研究業績

著　書
1) Parhar, S.I., and Sakuma, Y.: 〔共著〕視床下部【神経科学の基礎と臨床IV】第1 章　GnRH expression during development (脳の発達過程におけるGnRH遺伝子の発現). p. 1-19, ブレーン出版, 1995.

2) 上坂伸宏: 〔分担〕遺伝子病マニュアル(上)第20章ヘモグロビン異常症―鎌状赤血球症(ヘモグロビンS症). p. 362-363, 中山書店, 1995.

論　文
(1) 原著:
1) Takeo, T.1, Kudo, M.1, and Sakuma, Y(1Dept. of Physiology I, Hirosaki Univ. School of Medicine): Stria terminalis conveys a facilitatory estrogen effect on female rat lordosis reflex. Neurosci. Lett., 184 (2), 79-81, 1995.

2) Sakuma, Y.: Differential Control of Proceptive and Receptive Components of Female Rat Sexual Behavior by the Preoptic Area. Jpn. J. Physiol., 45 (3), 211-228, 1995.

3) Takeo, T.1, and Sakuma, Y.(1Dept. of Physiology I, Hirosaki Univ. School of Medicine): Diametrically opposite effects of estrogen on the excitability of female rat medial and lateral preoptic neurons with axons to the midbrain locomotor region. Neurosci. Res., 22 (1), 73-80, 1995.

4) Hasegawa, S.1, Hiruma, H.1, Uyesaka N., Noguchi, C.T.2, Schechter, A.N.2, and Rodgers, G.P.2(1Dept. of 3rd Internal Medicine, 2LCB/NIDDK/NIH): Filterability of Mixtures of Sickle and Normal Erythrocytes. Am. J. Hematol., 50, 91-97, 1995.

5) Wada-Kiyama, Y., and Kiyama, R.1(1Institute of Molecular and Cellular Biosciences, Univ. of Tokyo): Conservation and Periodicity of DNA Bend Sites in the Human b-Globin Gene Locus. J. Biol. Chem., 270, 12439-12445, 1995.

6) Kato, M.: Withdrawal of Somatostatin Augments L-type Ca2+ Current in Primary Cultured Rat Somatotrophs. J. Neuroendocrinol., 7, 855-859, 1995.

7) Kato, M.: Growth hormone-releasing hormone augments voltage-gated Na+ current in cultured rat pituitary cells. Am. J. Physiol., 270, C125-C130, 1996.

8) Ma, H.T.1, Kato, M., and Tatemoto, K.1(1Dept. of Molecular Physiology, Institute for Molecular and Cellular Regulation, Gunma Univ.): Effects of pancreastatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells. Regul. Peptides, 61, 143-148, 1996.

9) Kondo, Y., and Yamanouchi, K.1(1Neuroendocrinology, Sch. Human Sci., Waseda Univ.): The possible involvement of the nonstrial pathway of the amygdala in neural control of sexual behavior in male rats. Brain Res. Bull., 38 (1), 37-40, 1995.

10) Kondo, Y., and Arai, Y.1(1Dept. of Anatomy, Juntendo Univ.): Functional association between the medical amygdala and the medial preoptic area in regulation of mating behavior in the male rat. Physiol. Behav., 57 (1), 69-73, 1995.

11) Kato, A., and Kimura, F.1(1Dept. of Physiology, Yokohama Univ.): Electrophysiological studies on GnRH pulse generator of the orchidectomized rats: Central feedback control of gonadal steroids. Yokohama Med. J., 46 (2), 133-143, 1995.

12) Oonishi, T.1, Sakashita, K.1, Suematsu, N.2, Schechter, A.N.3, and Uyesaka, N.( 1The medical information institute, The Kanto Teishin hospital, 2Dept. of Pathology, The Yokufukai Hospital, 3LCB/NIDDK/NIH): Quantitative characterization of P- Glycoprotein-Mediated transport in mdr1-Gene-Transfected Lymphoma cells. Jpn. J. Physiol., 46 (1), 33-41, 1996.

13) Iino, M., Shimizu, M.1, Shichinohe, K.1, and Iida, K.2(1Dept. of Laboratory Animal Science, 2The Research Institute of Vaccine Therapy for Tumors and Infectious Diseases): Effect of alcohols on water diffusion across human erythrocyte membrane. Jpn. J. Clin. Comp. Hematol., 4 (2), 12-19, 1996.

14) Wada-Kiyama, Y., and Kiyam, R.1(1Institute of Molecular and Cellular Biosciences, Univ. of Tokyo): Conservation and Periodicity of DNA Bend Sites in Eukaryotic Genomes. DNA Res., 3, 25-30, 1996.

15) Saito, Y.1, Kato, M., Kobayashi, I.1, and Tatemoto, K.1(1Dept. of Laboratory Medicine and Clinical Laboratory Center, School of Medicine and Department of Molecular Physiology, Institute for Molecular and Cellular Regulation, Gunma Univ.): Effects of Bradykinin on the Intracellular Calcium Concentration of Pancreatic acinar AR42J Cells. Life Sci., 58 (18), 1569-1574, 1996.

16) Kato, M., Ma, H.T.1, and Tatemoto, K.1(1Dept. of Physiology, Institute for Molecular and Cellular Regulation, Gunma Univ.): GLP-1 depolarizes the rat pancreatic b cell in a Na+-dependent manner. Regul. Peptides, 1996.

(2) 総説:
1) 上坂伸宏: 電位依存性Na＋チャネルの生理機能と構造(特集: 人工膜と生体膜の接点をさぐる). 膜, 20(6), 398ー405, 1995.

2) 佐久間康夫: 雌ラット性行動の調節機構―性行動の中枢としての内側視索前野の役割. 医学のあゆみ, 176(8), 488-489, 1996.

3) 近藤保彦, 佐久間康夫: ペニス勃起―動物モデルと測定法. ヒューマンサンエンス, 8(2), 98-107, 1996.



学会発表
(1) シンポジウム:
1) Sakuma, Y.: Differential effects of estrogen on preoptic efferents to the "Reproductive brain" of the female rat.The second joint meeting of the physiological societies of Japan and U.K. and Eire, Symposium: Neuroendocrine Hypothalamus(Okazaki), 1995. 4.

2) Sakuma, Y.: Electrophysiological correlates of female rat sexual behavior: XXIV International Ethological Conference, Symposium: "Sexual Orientation I"(Honolulu, HI, U.S.A.), 1995. 8.

3) 近藤保彦, 佐久間康夫: ペニス勃起の高次脳神経制御: ラットの行動モデルからの検討.第6回日本病態生理学会総会シンポジウム「病態生理学から見た神経内分泌学」,1996. 1.

(2) 一般講演:
1) Suga, S.1, Nakano, K.1, Terao, T., and Sakuma, Y.(1Dept. of Physiol. I, Hirosaki Univ.): Facilitation of the lordosis reflex of female rats from the ventral premammillary nucleus.The 27th Annual Conference on Reproductive Behavior(Boston, MA, U.S.A.), 1995. 6.

2) Parhar, I.S., and Sakuma, Y.: Neuroanatomical distribution of growth hormone− releasing hormone(GHRH)along the migratory route of gonadotropin-releasing hormone (GnRH)neurons in the embryonic salmon. Fourth IBRO World Congress of Neuroscience (Kyoto), 1995. 7.

3) Kondo, Y., and Sakuma, Y.: Disruption of psychogenic but not reflexive erection in rats following medial amygdala lesions. Fourth IBRO World Congress of Neuroscience( Kyoto), 1995. 7.

4) Tashiro, S., and Sakuma, Y.: Time course of estrogen-induced excitability changes in ventromedial hypothalamic neurons with axons to the midbrain central gray. Fourth IBRO World Congress of Neuroscience(Kyoto), 1995. 7.

5) Uyesaka, N., Sogami, M.1, Era, S.2, Kato, K.3, Hasegawa, S., Usuki, T.3, Oonishi, T.3, and Schechter, A.N.4(1Dept. of Molecular Physiology, Fujita Health Univ., 2Dept. of Physiology II, Gifu Univ, 3Medical Information Institute, Kanto teisin Hospital, 4LCB/ NIDDK/NIH): Magnetization transfer characterization of red cells from patients with unstable hemoglobin disease. 9th International Congress of Biorheology(Montana, U.S.A., 1995. 7.

6) Uyesaka, N., Yamawaki, T.1, Oonishi, T.2, Kawa, T.1, Shio, H.3, and Fujino, T.4( 1Tsukasa Sokken Co., Ltd., 2Medical Information Institute, Kanto Teisin Hospital, 3The Shiga Medical Center for Adult Disease, 4Dept. of 1st Internal Medicine, Kyusyu Univ.): Rheologic characterization of nickel mesh filter by pressure-flow rate relationships of airflow. 9th International Congress of Biorheology(Montana, U.S.A.), 1995. 7.

7) Oonishi, T.1, Sakashita, K.1, Kumazaki, S.2, Katagiri, K.1, Suematsu, N.3, Ishihara, T.2, and Uyesaka, N.(1The Medical Information Institute, The Kanto Teishin Hospital, 2Dept. of Pulmonary Disease, The kanto Teishin Hospital, 3Dept. of Pathology, The Yokufukai Hospital): Impaired filterability of red blood cells from patients with chronic obstructive pulmonary disease.9th International Congress of Biorheology(Montana, U.S.A.), 1995. 7.

8) Wada-Kiyama, Y., and Kiyama, R.1(1Institute of Molecular and Cellular Biosciences, Univ. of Tokyo): Conservation and Periodicity of DNA Bend Sites in the Human b-Globin Gene Locus. Federation of American Societies for Experimental Biology- Genetic Recombination & Genome Rearrangements(Colorado, U.S.A.), 1995. 8.

9) Kondo, Y., Sachs, B.D.1, and Sakuma, Y.(1Dept. of Psychology, Univ. of Connecticut): Differential role of rat medial amygdala in the regulation of erection in three contexts. Society for Neuroscience 25th Annual Meeting(San Diego, CA, U.S.A.), 1995. 11.

10) Wada-Kiyama, Y.: An intrachromosomal repeating unit based on DNA bending of the human b-globin gene locus. The American Society of Hematology 37th Annual Meeting & Exposition(Washington, D.C., U.S.A.), 1995. 12.

11) Parhar, I.S., Yamada, S., and Sakuma, Y.: Developmental regulation of GnRH and CRH neurons in salmon during stress.Third Congress of Asia & Oceania Society for Comparative Endocrinology(Sydney, NSW, Australia), 1995. 12.

12) 飯野正昭, 清水真澄1, 七戸和博1(1実験動物): 水の赤血球膜拡散透過に対するアルコールの影響. 第92回日本薬理学会関東部会, 1995. 6.

13) 飯野正昭: 赤血球における磁化移動の解析. 第23回日本磁気共鳴医学会大会, 1995. 9.

14) 上坂伸宏: 異常ヘモグロビン赤血球の磁化移動の研究. 第23回日本磁気共鳴医学会大会, 1995. 9.

15) 木山裕子: ヒトβグロビン遺伝子座にみられるDNA折れ曲がりに基づいた染色体内繰り返しユニット. 第18回日本分子生物学会年会, 1995. 12.
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