Faculty Profiles - YOSHIMURA, Takashi

Editorial - The Japan Society for Comparative Endocrinology

Yoshimura Takashi, Ukena Kazuyoshi, Takei Yoshio

GENERAL AND COMPARATIVE ENDOCRINOLOGY Vol. 260 page： 162 - 163 2018.5

Identification of circadian clock modulators from existing drugs. International journal Open Access

T Katherine Tamai, Yusuke Nakane, Wataru Ota, Akane Kobayashi, Masateru Ishiguro, Naoya Kadofusa, Keisuke Ikegami, Kazuhiro Yagita, Yasufumi Shigeyoshi, Masaki Sudo, Taeko Nishiwaki-Ohkawa, Ayato Sato, Takashi Yoshimura

EMBO molecular medicine Vol. 10 ( 5 ) 2018.5

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

Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders.

DOI： 10.15252/emmm.201708724

Open Access

Seasonal reproduction: Photoperiodism, birds

Yusuke Nakane, Takashi Yoshimura

Encyclopedia of Reproduction page： 409 - 414 2018.1

Language：English Publishing type：Part of collection (book) Publisher：Elsevier

Seasonal changes in photoperiod are crucial cues for seasonal reproduction in birds inhabiting non-tropical regions. Birds possess photoreceptors in their eyes, pineal organs, and deep brain regions. It is known that birds detect light information of photoperiod, via deep brain photoreceptors. Several studies have revealed that photoinduced thyroid-stimulating hormone, originating from the pars tuberalis of the pituitary gland, prompt the local activation of thyroid hormone in the hypothalamus, which in turn leads to morphological changes in neurons and the secretion of gonadotropin-releasing hormone. In this article, we describe the mechanism for photoperiodism, using the seasonal reproduction of birds as an example.

DOI： 10.1016/B978-0-12-809633-8.20585-2

Seasonal Rhythms: The Role of Thyrotropin and Thyroid Hormones

Nakayama Tomoya, Yoshimura Takashi

THYROID Vol. 28 ( 1 ) page： 4 - 10 2018.1

Seasonal Regulation of Reproduction in Vertebrates: Special Focus on Avian Strategy

Shinomiya Ai, Yoshimura Takashi

REPRODUCTIVE AND DEVELOPMENTAL STRATEGIES: THE CONTINUITY OF LIFE page： 103 - + 2018

季節性と色覚－メダカの色覚は季節によってダイナミックに変化する Invited

新村毅，吉村崇

遺伝 Vol. 72 page： 617 - 622 2018

Dynamic plasticity in phototransduction regulates seasonal changes in color perception Open Access

Tsuyoshi Shimmura, Tomoya Nakayama, Ai Shinomiya, Shoji Fukamachi, Masaki Yasugi, Eiji Watanabe, Takayuki Shimo, Takumi Senga, Toshiya Nishimura, Minoru Tanaka, Yasuhiro Kamei, Kiyoshi Naruse, Takashi Yoshimura

NATURE COMMUNICATIONS Vol. 8 ( 1 ) 2017.12

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

To cope with seasonal changes in the environment, organisms adapt their physiology and behavior. Although color perception varies among seasons, the underlying molecular basis and its physiological significance remain unclear. Here we show that dynamic plasticity in phototransduction regulates seasonal changes in color perception in medaka fish. Medaka are active and exhibit clear phototaxis in conditions simulating summer, but remain at the bottom of the tank and fail to exhibit phototaxis in conditions simulating winter. Mate preference tests using virtual fish created with computer graphics demonstrate that medaka are more attracted to orange-red-colored model fish in summer than in winter. Transcriptome analysis of the eye reveals dynamic seasonal changes in the expression of genes encoding photopigments and their downstream pathways. Behavioral analysis of photopigment-null fish shows significant differences from wild type, suggesting that plasticity in color perception is crucial for the emergence of seasonally regulated behaviors.

DOI： 10.1038/s41467-017-00432-8

Open Access

The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models. International journal Open Access

Keisuke Ikegami, Takashi Yoshimura

Best practice & research. Clinical endocrinology & metabolism Vol. 31 ( 5 ) page： 475 - 485 2017.10

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

Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms.

DOI： 10.1016/j.beem.2017.09.002

Open Access

Molecular mechanism regulating seasonality Reviewed

Keisuke Ikegami, Takashi Yoshimura

Biological Timekeeping: Clocks, Rhythms and Behaviour page： 589 - 605 2017.1

Language：English Publishing type：Part of collection (book) Publisher：Springer (India) Private Ltd.

The mechanisms of vertebrate seasonal time measurement were a mystery for a long time, but recent comparative studies have uncovered the photoperiodic signal transduction cascades in birds, mammals, and fish. These studies reveal the universality and diversity of photoperiodic mechanisms. That is, the molecules involved are conserved, while the tissues responsible for these mechanisms are different in different species (Nakane and Yoshimura, Front Neurosci 8:115, 2014). It is well established that the circadian clock is involved in photoperiodic time measurement. However, the underlying mechanism that defines the photoinducible phase or critical photoperiod (i.e., how organisms measure day length using a circadian clock) is at the heart of photoperiodic time measurement, and this question remains to be answered by future studies.

DOI： 10.1007/978-81-322-3688-7_28

Molecular and neuroendocrine mechanisms of avian seasonal reproduction

T. Katherine Tamai, Takashi Yoshimura

Advances in Experimental Medicine and Biology Vol. 1001 page： 125 - 136 2017

Language：English Publishing type：Part of collection (book) Publisher：Springer New York LLC

Animals living outside tropical zones experience seasonal changes in the environment and accordingly, adapt their physiology and behavior in reproduction, molting, and migration. Subtropical birds are excellent models for the study of seasonal reproduction because of their rapid and dramatic response to changes in photoperiod. For example, testicular weight typically changes by more than a 100-fold. In birds, the eyes are not necessary for seasonal reproduction, and light is instead perceived by deep brain photoreceptors. Functional genomic analysis has revealed that long day (LD)-induced thyrotropin from the pars tuberalis of the pituitary gland causes local thyroid hormone (TH) activation within the mediobasal hypothalamus. This local bioactive TH, triiodothyronine (T3), appears to regulate seasonal gonadotropin-releasing hormone (GnRH) secretion through morphological changes in neuro-glial interactions. GnRH, in turn, stimulates gonadotropin secretion and hence, gonadal development under LD conditions. In marked contrast, low temperatures accelerate short day (SD)-induced testicular regression in winter. Interestingly, low temperatures increase circulating levels of T3 to support adaptive thermogenesis, but this induction of T3 also triggers the apoptosis of germ cells by activating genes involved in metamorphosis. This apparent contradiction in the role of TH has recently been clarified. Central activation of TH during spring results in testicular growth, while peripheral activation of TH during winter regulates adaptive thermogenesis and testicular regression.

DOI： 10.1007/978-981-10-3975-1_8

The Hypothalamo-Pituitary-Thyroid (HPT)-axis: Animal Studies. (in press) Invited Reviewed Open Access

Ikegami K, Yoshimura T

Best Practice & Research Clinical Endocrinology & Metabolism 2017

組織特異的TSH糖鎖修飾 Invited Reviewed

池上啓介, 吉村崇

月刊Mebio Vol. 33 page： 11 - 18 2016.9

Molecular basis for regulating seasonal reproduction in vertebrates Invited Reviewed Open Access

Nishiwaki-Ohkawa T, Yoshimura T

Journal of Endocrinology Vol. 229 ( 3 ) page： R117 - R127 2016.6

Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction. Reviewed International journal

Keisuke Ikegami, Takashi Yoshimura

General and comparative endocrinology Vol. 227 page： 64 - 68 2016.2

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

Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms.

DOI： 10.1016/j.ygcen.2015.05.009