Comprehensive studies of androgen and SARM as a background of onset or treatment of life-related diseases

• Project/Area Number: 15H04854
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Fukuoka University
• Principal Investigator: Yanase Toshihiko 福岡大学, 医学部, 教授 (30239818)
• Co-Investigator(Renkei-kenkyūsha): NOMIYAMA Takashi 福岡大学, 医学部, 准教授 (10532559) ; TANABE Makito 福岡大学, 医学部, 講師 (60707305) ; TANAKA Tomoko 福岡大学, 生活習慣病制御講座講座, 助教 (10380528)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 選択的アンドロゲン受容体修飾剤 / テストステロン / 前立腺癌 / LOH症候群 / メタボリックシンドローム / 生活習慣病 / アンドロゲン / LOH / アドロゲン

Outline of Final Research Achievements

The following actions of a SARM, S42 were clarified;(1)from array analysis of mouse tissues loaded with high fat diet, the induction of catecholamine synthesis enzymes and GLUT4 expression in liver and visceral adipose tissue may be related to the anti-obesity action of S42, (2)from the investigations using cultured myotubes and orchiectomy mouse, S42 may act on catabolism suppression and synthesis promotion of muscle proteins, (3)S42 inhibits proliferation of castration-sensitive human prostate cancer cell lines in vitro and in vivo. Regarding the clinical significance of testosterone(T), the usefulness of the total T value as a diagnostic index of metabolic syndrome and no relationship between various T values and total score of questionnaire AMS in LOH (late-onset hypogonadism) examination were clarified.From the relationship between insulin resistance and AMS score, increased AMS score in LOH may reflect low grade inflammation caused by insulin resistance.

Research Products

• [Journal Article] Clinical Investigation of Adrenal Incidentalomas in Japanese Patients of the Fukuoka Region with Updated Diagnostic Criteria for Sub-clinical Cushing's Syndrome (2018)
  • Author(s): Abe, I., Sugimoto, K., Miyajima, T., Ide, T., Minezaki, M., Takeshita, K., Takahara, S., Nakagawa, M., Fujimura, Y., Kudo, T., et al.
  • Journal Title: Internal Medicine Volume: 57 Issue: 17 Pages: 2467-2472
  • DOI: 10.2169/internalmedicine.0550-17
  • NAID: 130007480015
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-09-01
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selective Androgen Receptor Modulator S42 Suppresses Prostate Cancer Cell Proliferation. (2018)
  • Author(s): Kawanami, T., Tanaka, T., Hamaguchi, Y., Nomiyama, T., Nawata, H., and Yanase, T.
  • Journal Title: Endocrinology Volume: 159 Issue: 4 Pages: 1774-1792
  • DOI: 10.1210/en.2018-00099
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HMGA1a induces alternative splicing of estrogen receptor alpha in MCF-7 human breast cancer cells. (2018)
  • Author(s): Ohe, K., Miyajima, S., Abe, I., Tanaka, T., Hamaguchi, Y., Harada, Y., Horita, Y., Beppu, Y., Ito, F., Yamasaki, T., et al.
  • Journal Title: J Steroid Biochem Mol Biol Volume: 印刷中 Pages: 21-26
  • DOI: 10.1016/j.jsbmb.2018.04.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New diagnostic criteria of adrenal subclinical Cushing’s syndrome: opinion from the Japan Endocrine Society (2018)
  • Author(s): Yanase, T., Oki, Y., Katabami, T., Otsuki, M., Kageyama, K., Tanaka, T., Kawate, H., Tanabe, M., Doi, M., Akehi, Y., et al.
  • Journal Title: Endocrine Journal Volume: 65 Issue: 4 Pages: 383-393
  • DOI: 10.1507/endocrj.EJ17-0456
  • NAID: 130006727070
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Frailty in elderly diabetes patients (2018)
  • Author(s): Yanase, T., Yanagita, I., Muta, K., and Nawata, H.
  • Journal Title: Endocrine Journal Volume: 65 Issue: 1 Pages: 1-11
  • DOI: 10.1507/endocrj.EJ17-0390
  • NAID: 130006321954
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Accuracy of adrenal computed tomography in predicting the unilateral subtype in young patients with hypokalaemia and elevation of aldosterone in primary aldosteronism. (2018)
  • Author(s): Umakoshi, H., Ogasawara, T., Takeda, Y., Kurihara, I., Itoh, H., Katabami, T., Ichijo, T., Wada, N., Shibayama, Y., Yoshimoto, T., et al.
  • Journal Title: Clin Endocrinol (Oxf) Volume: 88 Issue: 5 Pages: 645-651
  • DOI: 10.1111/cen.13582
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence of Cardiovascular Disease and Its Risk Factors in Primary Aldosteronism: A Multicenter Study in Japan. (2018)
  • Author(s): Ohno, Y., Sone, M., Inagaki, N., Yamasaki, T., Ogawa, O., Takeda, Y., Kurihara, I., Itoh, H., Umakoshi, H., Tsuiki, M., et al.
  • Journal Title: Hypertension Volume: 71 Issue: 3 Pages: 530-537
  • DOI: 10.1161/hypertensionaha.117.10263
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low glycated hemoglobin level is associated with severity of frailty in Japanese elderly diabetes patients. (2018)
  • Author(s): Yanagita, I., Fujihara, Y., Eda, T., Tajima, M., Yonemura, K., Kawajiri, T., Yamaguchi, N., Asakawa, H., Nei, Y., Kayashima, Y., et al.
  • Journal Title: J Diabetes Investig Volume: 9 Issue: 2 Pages: 419-425
  • DOI: 10.1111/jdi.12698
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A higher score on the Aging Males’ Symptoms scale is associated with insulin resistance in middle-aged men (2017)
  • Author(s): Hamanoue, N., Tanabe, M., Tanaka, T., Akehi, Y., Murakami, J., Nomiyama, T., and Yanase, T.
  • Journal Title: Endocrine Journal Volume: 64 Issue: 5 Pages: 521-530
  • DOI: 10.1507/endocrj.EJ16-0619
  • NAID: 130005682812
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of metabolic disorders on prostate cancer growth: Androgen and insulin resistance perspectives. (2017)
  • Author(s): Yanase, T., Kawanami, T., Tanaka, T., Tanabe, M., and Nomiyama, T.
  • Journal Title: Reprod Med Biol Volume: 16 Issue: 3 Pages: 252-257
  • DOI: 10.1002/rmb2.12039
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-kappaB Activation. (2017)
  • Author(s): Iwaya, C., Nomiyama, T., Komatsu, S., Kawanami, T., Tsutsumi, Y., Hamaguchi, Y., Horikawa, T., Yoshinaga, Y., Yamashita, S., Tanaka, T., et al.
  • Journal Title: Endocrinology Volume: 158 Issue: 12 Pages: 4218-4232
  • DOI: 10.1210/en.2017-00461
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Postpartum hypothalamic adrenal insufficiency with remission: A rare case (2017)
  • Author(s): Akehi, Y., Hashimoto, Y., Meren, J., Tanabe, M., Nomiyama, T., and Yanase, T.
  • Journal Title: Endocrine Journal Volume: 64 Issue: 2 Pages: 157-162
  • DOI: 10.1507/endocrj.EJ16-0066
  • NAID: 130005397091
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: A retrospective cohort study using a Japanese hospital database. (2017)
  • Author(s): Tanabe, M., Motonaga, R., Terawaki, Y., Nomiyama, T., and Yanase, T.
  • Journal Title: J Diabetes Investig Volume: 8 Issue: 2 Pages: 227-234
  • DOI: 10.1111/jdi.12567
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Augmented GH secretion and Stat3 phosphorylation in an aryl hydrocarbon receptor interacting protein (AIP)-disrupted somatotroph cell line. (2016)
  • Author(s): Fukuda T, Tanaka T, Hamaguchi Y, Kawanami T, Nomiyama T, Yanase T
  • Journal Title: PLOS ONE Volume: 11(10) Issue: 10 Pages: e0164131-e0164131
  • DOI: 10.1371/journal.pone.0164131
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calibration and evaluation of routine methods by serum certified reference material for aldosterone measurement in blood (2016)
  • Author(s): Nishikawa T, Omura M, Kawaguchi M, Takatsu A, Satoh F, Ito S, Kurihara I, Itoh H, Yanase T, Shibata H, Oki Y, Naruse M, Sakurai K, Sasamoto H, Kuwa K.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 12 Pages: 1065-1080
  • DOI: 10.1507/endocrj.EJ16-0304
  • NAID: 130005180830
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation. (2016)
  • Author(s): Morooka N, Ueguri K, Yee KK, Yanase T, Sato T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 477(4) Issue: 4 Pages: 895-901
  • DOI: 10.1016/j.bbrc.2016.06.155
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline [Opinion] (2016)
  • Author(s): Yanase T, Tajima T, Katabami T, Iwasaki Y, Tanahashi Y, Sugawara A, Hasegawa T, Mune T, Oki Y, Nakagawa Y, Miyamura N, Shimizu C, Otsuki M, Nomura M, Akehi Y, Tanabe M, Kasayama S.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 9 Pages: 765-784
  • DOI: 10.1507/endocrj.EJ16-0242
  • NAID: 130005597967
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve. (2016)
  • Author(s): Dong Z, Huang M, Liu Z, Xie P, Dong Y, Wu X, Qu Z, Shen B, Huang X, Zhang T, Li J, Liu J, Yanase T, Zhou C, Xu Y.
  • Journal Title: Cell Death Differ. Volume: 23(10) Issue: 10 Pages: 1602-1614
  • DOI: 10.1038/cdd.2016.47
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of miR-146aC>G, miR-149C>T, miR-196a2T>C, and miR-499A>G polymorphisms with risk of recurrent implantation failure in Korean women. (2016)
  • Author(s): Cho SH, Chung KW, Kim JO, Jang H, Yoo JK, Choi Y, Ko JJ, Kim JH, Nishi Y, Yanase T, Lee WS, Kim NK.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 202 Pages: 14-19
  • DOI: 10.1016/j.ejogrb.2016.04.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] T GLP-1 receptor agonist as treatment for cancer as well as diabetes: beyond blood glucose control. (2016)
  • Author(s): Nomiyma T, Yanase T.
  • Journal Title: Expert Review of Endocrinology & Metabolism Volume: 11 Pages: 357-364
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 特集：糖尿病と腎泌尿器疾患 テストステロンと糖尿病 (2016)
  • Author(s): 柳瀬敏彦
  • Journal Title: 腎臓内科・泌尿器科 Volume: 3(6) Pages: 603-609
• [Journal Article] 特集：男性のアンチエイジングとテストステロン テストステロンと肥満 (2016)
  • Author(s): 柳瀬敏彦
  • Journal Title: 日本抗加齢医学雑誌 Volume: 12(3) Pages: 340-347
• [Journal Article] 男性骨粗鬆症における選択的アンドロゲン受容体モジュレーター (ＳＡＲＭ)の可能性 (2016)
  • Author(s): 柳瀬敏彦
  • Journal Title: CLINICAL CALCIUM Volume: 26(7) Pages: 1023-1030
• [Journal Article] Total testosterone is the most valuable indicator of metabolic syndrome among various testosterone values in middle-aged Japanese men (2015)
  • Author(s): Tanabe M, Akehi Y, Nomiyama T, Murakami J, Yanase T.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 123-132
  • DOI: 10.1507/endocrj.EJ14-0313
  • NAID: 130004700286
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Combined treatment with Extendin-4 and metoformin attenuates prostate cancer growth. (2015)
  • Author(s): Tsutumi Y, Nomiyama T, Kawanami T, Hamaguchi Y, Tanaka T, Murase K, Motonaga R, Tanabe M, Yanase T.
  • Journal Title: PLOS ONE Volume: 10 Issue: 10 Pages: e0139709-e0139709
  • DOI: 10.1371/journal.pone.0139709
  • Peer Reviewed / Open Access
• [Journal Article] Dehydroepiandrosterone-enhanced dual specificity protein phosphatase (DDSP) prevents diet-induced and genetic obesity. (2015)
  • Author(s): Watanabe T, Ashida K, Goto K, Nawata H, Takayanagi R, Yanase T, Nomura M
  • Journal Title: Biochem Biophys Res Commun Volume: 468 Issue: 1-2 Pages: 196-201
  • DOI: 10.1016/j.bbrc.2015.10.131
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TYK2 Promoter Variant and Diabetes Mellitus in the Japanese. (2015)
  • Author(s): Nagafuchi S, Kamada-Hibio Y, Hirakawa K, Tsutsu N, Minami M, Okada A, Kai K, Teshima M, Moroishi A, Murakami Y, Umeno Y, Yokogawa Y, Kogawa K, Izumi K, Anzai K, Iwakiri R, Hamaguchi K, Sasaki N, Nohara S, Yoshida E, Harada M, Akashi K, Yanase T, Ono J, Okeda T, Fujimoto R, Ihara K, et al.
  • Journal Title: EbioMedicine Volume: 2 Issue: 7 Pages: 744-749
  • DOI: 10.1016/j.ebiom.2015.05.004
  • Peer Reviewed / Open Access
• [Journal Article] Reduced vascular events in type 2 diabetes by biguanide relative to sulfonylurea: study in a Japanese Hospital Database. (2015)
  • Author(s): Tanabe M, Nomiyama T, Motonaga R, Murase K, Yanase T.
  • Journal Title: BMC Endocr Disord. Volume: 15 Issue: 1 Pages: 48-48
  • DOI: 10.1186/s12902-015-0045-y
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes undergoing hemodialysis. (2015)
  • Author(s): Terawaki Y, Nomiyama T, Takahashi H, Tsutsumi Y, Murase K, Nagaishi R, Tanabe M, Kudo T, Kobayashi K, Yasuno T, Nakashima H, Yanase T.
  • Journal Title: Diabetol Metab Syndr. Volume: 7 Issue: 1 Pages: 44-44
  • DOI: 10.1186/s13098-015-0043-2
  • Peer Reviewed / Open Access
• [Presentation] Androgen and metabolic syndrome. (2017)
  • Author(s): Yanase T.
  • Organizer: The 8th Congress of the International Society for Gender Medicine
  • Int'l Joint Research / Invited
• [Presentation] アンドロゲン受容体作動薬S42の前立腺癌細胞増殖に対する影響 (2017)
  • Author(s): 川波賢子、田中智子、Liu Min、野見山崇、名和田新、柳瀬敏彦
  • Organizer: 第90回日本内分泌学会学術集会
• [Presentation] 特別講演「生活習慣病（メタボ、糖尿病、高血圧）に潜むステロイド関連疾患」 (2016)
  • Author(s): 柳瀬敏彦
  • Organizer: 第24回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 大分市
  • Year and Date: 2016-12-03
  • Invited
• [Presentation] 特別講演II 女性におけるアンドロゲンとは？ (2016)
  • Author(s): 柳瀬敏彦
  • Organizer: 第16回日本Men's Health医学会、第7回テストステロン研究会
  • Place of Presentation: 札幌市
  • Year and Date: 2016-07-08
  • Invited
• [Presentation] 教育講演 「内分泌・代謝学の視点からみたステロイドホルモン療法：前立腺癌治療におけるピットフォール」 (2016)
  • Author(s): 柳瀬敏彦
  • Organizer: 第35回日本アンドロロジー学会
  • Place of Presentation: 前橋市
  • Year and Date: 2016-06-24
  • Invited
• [Presentation] シンポジウム1 テストステロンの臨床的諸問題「メタボリックシンドロームにおける各種アンドロゲン指標の検討」 (2015)
  • Author(s): 柳瀬敏彦
  • Organizer: 第34回日本アンドロロジー学会、第22回精巣毒性研究会
  • Place of Presentation: 福岡
  • Year and Date: 2015-06-26
• [Book] 選択的アンドロゲン受容体モジュレーター(SARM)サルコペニア治療への応用 サルコペニアとフレイル（医療職間連携による多角的アプローチ） (2015)
  • Author(s): 柳瀬敏彦
  • Total Pages: 8
  • Publisher: 医薬ジャーナル社