Updated on 2025/08/29

写真a

 
Fujisawa Satoshi
 
Organization
Scheduled update Special-Appointment Assistant Professor
Position
Special-Appointment Assistant Professor
Contact information
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Degree

  • 社会健康医学修士 (専門職) ( 2024.3   京都大学大学院 )

  • 博士 (医学) ( 2019.6   岡山大学大学院 )

Research Interests

  • 患者報告アウトカム

  • 内科学

  • 内分泌学

Research Areas

  • Life Science / General internal medicine

  • Life Science / Metabolism and endocrinology

Education

  • Kyoto University   大学院医学研究科 社会健康医学系専攻   専門職学位課程

    2022.4 - 2024.3

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  • 岡山大学大学院   医歯薬学総合研究科   博士課程

    2015.4 - 2019.6

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  • Okayama University   医学部   医学科

    2005.4 - 2011.3

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Research History

  • 岡山大学病院   助教

    2024.4

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  • 岡山大学病院   医員

    2023.5 - 2024.3

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  • Okayama University Hospital   内分泌センター

    2016.11 - 2022.3

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  • Okayama University Hospital   腎臓・糖尿病・内分泌内科

    2015.4 - 2016.3

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Committee Memberships

  • 日本腎臓学会   CKD診療ガイドライン改訂委員会 SR委員  

    2021   

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Papers

  • Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells. International journal

    Yoshihiko Itoh, Kenichi Inagaki, Tomohiro Terasaka, Eisaku Morimoto, Takahiro Ishii, Kimitomo Yamaoka, Satoshi Fujisawa, Jun Wada

    International journal of molecular sciences   26 ( 14 )   2025.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling.

    DOI： 10.3390/ijms26146927

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  • Effects of Wnt-β-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells. International journal

    Eisaku Morimoto, Kenichi Inagaki, Motoshi Komatsubara, Tomohiro Terasaka, Yoshihiko Itoh, Satoshi Fujisawa, Erika Sasaki, Yuki Nishiyama, Takayuki Hara, Jun Wada

    Journal of the Endocrine Society   6 ( 10 )   bvac121   2022.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    Pheochromocytomas and paragangliomas (PPGLs) are classified into 3 major categories with distinct driver genes: pseudohypoxia, kinase signaling, and Wnt-altered subtypes. PPGLs in the Wnt-altered subtype are sporadic and tend to be aggressive with metastasis, where somatic gene fusions affecting mastermind-like 3 (MAML3) and somatic mutations in cold shock domain containing E1 (CSDE1) cause overactivation of Wnt-β-catenin signaling. However, the relation between Wnt-β-catenin signaling and the biological behavior of PPGLs remains unexplored. In rat pheochromocytoma PC12 cells, Wnt3a treatment enhanced cell proliferation and suppressed mRNA expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, and dopamine secretion. We identified the expression of sclerostin in PC12 cells, which is known as an osteocyte-derived negative regulator for Wnt signaling-driven bone formation. Inhibition of endogenous Wnt pathway by XAV939 or sclerostin resulted in attenuated cell proliferation and increased TH expression. Furthermore, Wnt3a pretreatment suppressed bone morphogenetic protein (BMP)-induced Smad1/5/9 phosphorylation whereas BMPs enhanced sclerostin expression in PC12 cells. In the Wnt-altered subtype, the increased Wnt-β-catenin pathway may contribute the aggressive clinical behavior with reduced catecholamine production. Furthermore, upregulated expression of sclerostin by BMPs may explain the osteolytic metastatic lesions observed in metastatic PPGLs.

    DOI： 10.1210/jendso/bvac121

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  • Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells. International journal

    Yoshiaki Soejima, Nahoko Iwata, Nanako Nakayama, Shinichi Hirata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Kohei Oguni, Takahiro Nada, Satoshi Fujisawa, Fumio Otsuka

    International journal of molecular sciences   23 ( 17 )   2022.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope LβT2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LHβ and FSHβ mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in LβT2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in LβT2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells.

    DOI： 10.3390/ijms23179782

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  • 【指定難病Up to Date】ビタミンD抵抗性くる病・骨軟化症 特にFGF23関連低リン血症性くる病・骨軟化症について

    藤澤 諭, 稲垣 兼一, 和田 淳

    岡山医学会雑誌   134 ( 2 )   92 - 94   2022.8

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    Language：Japanese   Publisher：岡山医学会  

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  • Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism. International journal

    Natsumi Uchiyama-Matsuoka, Kenji Tsuji, Haruhito A Uchida, Shinji Kitamura, Yoshihiko Itoh, Yuki Nishiyama, Eisaku Morimoto, Satoshi Fujisawa, Tomohiro Terasaka, Takayuki Hara, Kanako Ogura-Ochi, Kenichi Inagaki, Jun Wada

    Frontiers in endocrinology   13   1048863 - 1048863   2022

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    Language：English   Publishing type：Research paper (scientific journal)  

    INTRODUCTION: While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism. METHODS: Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. RESULTS: Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 m2) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m2). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. CONCLUSIONS: We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.

    DOI： 10.3389/fendo.2022.1048863

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  • Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells. International journal

    Satoshi Fujisawa, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Takahiro Nada, Jun Wada, Fumio Otsuka

    International journal of molecular sciences   22 ( 9 )   2021.4

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.

    DOI： 10.3390/ijms22094553

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  • Parathyroid Lipoadenoma: A Pitfall in Preoperative Localization.

    Satoshi Fujisawa, Kenichi Inagaki, Jun Wada

    Internal medicine (Tokyo, Japan)   58 ( 8 )   1183 - 1184   2019.4

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.2169/internalmedicine.1249-18

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  • Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells. International journal

    Satoshi Fujisawa, Motoshi Komatsubara, Kanako Ogura-Ochi, Naoko Tsukamoto-Yamauchi, Kishio Toma, Kenichi Inagaki, Jun Wada, Fumio Otsuka

    Peptides   113   35 - 40   2019.3

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    The impact of orexins on anterior pituitary function has yet to be clarified. We studied the effects of orexin A and its interaction with the bone morphogenetic protein (BMP) system on the regulatory role of prolactin synthesis using rat lactotrope GH3 cells expressing BMP-4. Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells. Orexin A suppressed forskolin-induced, but not basal, prolactin mRNA expression without reducing cAMP levels. Of note, orexin A suppressed BMP-4-induced prolactin mRNA and cAMP synthesis. Impairment of the effects of orexin by chemical inhibitors suggested involvement of the P38 pathway in the OX1R activity that suppresses BMP-4-induced PRL expression. Given that inhibition of BMP-receptor signaling reduced prolactin mRNA levels, endogenous BMP action is likely to be linked to the activation of prolactin synthesis by GH3 cells. Orexin A was revealed to suppress Smad1/5/9 phosphorylation and Id-1 transcription induced by BMP-4, which was restored in the presence of orexin-receptor antagonists, suggesting that the inhibitory effect of orexin A occurred via OX1R. Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression. These results indicated that orexin A plays an inhibitory role in prolactin production through suppression of endogenous BMP activity in GH3 cells, suggesting that a new functional role of the interaction between orexin and BMP-4 is modulation of prolactin levels in lactotrope cells.

    DOI： 10.1016/j.peptides.2019.01.002

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  • Interaction between orexin A and bone morphogenetic protein system on progesterone biosynthesis by rat granulosa cells. International journal

    Shiho Fujita, Toru Hasegawa, Yuki Nishiyama, Satoshi Fujisawa, Yasuhiro Nakano, Takahiro Nada, Nahoko Iwata, Yasuhiko Kamada, Hisashi Masuyama, Fumio Otsuka

    The Journal of steroid biochemistry and molecular biology   181   73 - 79   2018.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    The involvement of orexins in reproductive function has been gradually uncovered. However, the functional role of orexins in ovarian steroidogenesis remains unclear. In the present study, we investigated the effects of orexin A on ovarian steroidogenesis by using rat primary granulosa cells that express both OX1 and OX2 receptors for orexins. Treatment with orexin A enhanced progesterone, but not estradiol, biosynthesis induced by FSH, whereas it did not affect basal levels of progesterone or estradiol. In accordance with the effects on steroidogenesis, orexin A increased the mRNA levels of progesterogenic enzymes, including StAR, P450scc and 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH. Under the condition of blockage of endogenous BMP actions by noggin or BMP-signaling inhibitors, orexin A failed to increase levels of progesterone synthesis induced by FSH treatment, suggesting that endogenous BMP activity in granulosa cells might be involved in the enhancement of progesterone synthesis by orexin A. Treatment with orexin A impaired Smad1/5/9 activation as well as Id-1 mRNA expression stimulated by BMP-6 and BMP-7, the latter of which was reversed by treatment with an OX1 antagonist. It was also found that orexin A suppressed the mRNA expression of both type-I and -II receptors for BMPs and increased that of inhibitory Smad6 and Smad7 in granulosa cells. On the other hand, treatments with BMP-6 and -7 suppressed the expression of OX1 and OX2. Collectively, the results indicated that orexin A enhances FSH-induced progesterone production, at least in part, by downregulating BMP signaling in granulosa cells. Thus, a new role of orexin A in facilitating progesterone synthesis and functional interaction between the orexin and BMP systems in granulosa cells were revealed.

    DOI： 10.1016/j.jsbmb.2018.03.004

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  • Isolated Follicle-stimulating Hormone Deficiency Coincidentally Diagnosed by Hematospermia.

    Satoshi Fujisawa, Fumio Otsuka

    Internal medicine (Tokyo, Japan)   57 ( 12 )   1799 - 1799   2018.6

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.2169/internalmedicine.9693-17

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  • Colonoscopy examination requires a longer time in patients with acromegaly than in other individuals.

    Masaya Iwamuro, Miho Yasuda, Kou Hasegawa, Satoshi Fujisawa, Kanako Ogura-Ochi, Yuusaku Sugihara, Keita Harada, Sakiko Hiraoka, Hiroyuki Okada, Fumio Otsuka

    Endocrine journal   65 ( 2 )   151 - 157   2018.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    This study aimed to determine the prevalence of colorectal neoplasms and to investigate the rate of and time required for cecal intubation in patients with acromegaly. A database search performed at our institution identified 29 patients with acromegaly who underwent colonoscopy. Data regarding the endoscopic, biological, and pathological examinations performed were retrospectively reviewed from the clinical records. Subsequently, the rate of and time required for cecal intubation were investigated in 23 patients with acromegaly and compared with the corresponding data of the control group. Control subjects were selected from a 2:1 matched historical control cohort, according to baseline characteristics. The mean age of the acromegaly group (17 female and 12 male) was 60.4 ± 12.6 years. Twelve patients had adenoma (41.4%), eight patients had hyperplastic polyps (27.6%), three patients had sessile serrated adenoma/polyps (10.3%), and three patients had colon cancer (10.3%). Successful cecal intubation was achieved in all patients in both groups. The difference in the time required for successful intubation between the acromegaly group (15.7 ± 9.8 minutes) and the control group (8.7 ± 6.0 minutes) was statistically significant. Linear regression analysis revealed that increased patient age was significantly related to longer colonoscope insertion times. In conclusion, although cecal intubation during colonoscopy was successful in all participants, it required a longer time in patients with acromegaly. Our results underscore the importance of and certain technical difficulties involved in colonoscopy procedures in patients with acromegaly, especially in older patients.

    DOI： 10.1507/endocrj.EJ17-0322

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  • Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells. International journal

    Kanako Ogura-Ochi, Satoshi Fujisawa, Nahoko Iwata, Motoshi Komatsubara, Yuki Nishiyama, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Jun Wada, Fumio Otsuka

    Peptides   94   19 - 24   2017.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells.

    DOI： 10.1016/j.peptides.2017.06.001

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  • A unique acromegalic osteoarthropathy: manubriosternal joint arthritis. International journal

    Satoshi Fujisawa, Fumio Otsuka

    Clinical case reports   5 ( 5 )   725 - 726   2017.5

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Osteoarthritis of the manubriosternal joint can be found in patients with inflammatory arthritis. Acromegalic arthropathy is often found in the shoulders, wrists, knees, hips, and spine; however, attention should also be given to sternalgia as a complication of acromegalic involvement of the manubriosternal joint.

    DOI： 10.1002/ccr3.913

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Books

  • 内科学書第９版

    藤澤諭, 大塚文男（ Role： Contributor ,  視床下部の異常・視床下部の検査法）

    中山書店  2019.8 

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Awards

  • Clinical Endocrinology KO Rounds Runners-up

    2025.6   第98回日本内分泌学会学術総会  

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  • ロシュ若手奨励賞 (Young Investigative Award)

    2024.10   第67回日本甲状腺学会学術総会  

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  • 優秀賞

    2024.3   京都大学 大学院 医学研究科 社会健康医学系専攻  

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  • トラベルグラント

    2019.10   第62回日本甲状腺学会学術集会  

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  • 令和元年度大藤内分泌医学賞

    2019.9  

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  • 若手研究奨励賞

    2019.9   第20回日本内分泌学会中国支部学術集会  

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  • 平成30年度大藤内分泌医学賞

    2018.8  

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  • 最優秀発表賞

    2018.8   日本下垂体研究会第33回学術集会  

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