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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
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)...
May 2018: EMBO Molecular Medicine
Naoki Horii, Koji Sato, Noboru Mesaki, Motoyuki Iemitsu
Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA), a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT) synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats...
2016: PloS One
Koji Sato, Motoyuki Iemitsu, Keisho Katayama, Koji Ishida, Yoji Kanao, Mitsuru Saito
Previous studies have shown that acute exercise elevates sex steroid hormone concentrations in rodents and that sprint exercise increases circulating testosterone in healthy young men. However, the effect of different exercise intensities on sex steroid hormone responses at different levels of physical fitness is still unclear. In this study, we compared circulating sex steroid hormone responses at different exercise intensities in athletes and non-athletes. Eight male endurance athletes and 11 non-athletes performed two 15 min sessions of submaximal exercise at 40 and 70% peak oxygen uptake (V̇(O2peak)), respectively, and exercised at 90% V̇(O2peak) until exhaustion...
January 2016: Experimental Physiology
N Horii, K Sato, N Mesaki, M Iemitsu
Administration of dehydroepiandrosterone (DHEA), a precursor of sex steroid hormones, reduces total and visceral fat mass and elevates adipocytic adiponectin gene expression. The aim of this study is to investigate whether levels of peroxisome proliferator-activated receptors (PPARs) in muscle and transcription of PPAR target genes are affected by long-term DHEA administration or exercise training, and whether altered PPAR levels are associated with circulating adiponectin level in obese rats. After 14 weeks on a high-sucrose diet, obese male Wistar rats were assigned randomly to one of 3 groups: control, DHEA administration (1 mg/kg body weight), or exercise training (treadmill running for 1 h, 25 m/min, 5 days/week) for 6 weeks (n=7 for each group)...
March 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Takumi Yokokawa, Koji Sato, Nobumasa Iwanaka, Hiroki Honda, Kazuhiko Higashida, Motoyuki Iemitsu, Tatsuya Hayashi, Takeshi Hashimoto
Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5'-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear...
July 17, 2015: Biochemical and Biophysical Research Communications
Kenji Takeuchi, Hirohiko Goto, Yuko Ito, Makoto Sato, Satoshi Matsumoto, Tadashi Senba, Hideyuki Yamada, Ken Umehara
The effects of the peroxisome proliferator, dehydroepiandrosterone sulfate (DHEAS), and the typical cytochrome P450 (CYP) inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) on fatty liver were examined in rats. Treating rats with orotic acid caused marked accumulation of lipid droplets in the liver. This effect of orotic acid was almost eradicated by co-treatment with DHEAS and PB. While DHEAS or PB alone also alleviated fatty liver, treatment with 3-MC caused little effect on a reduction in lipid droplets...
April 2015: Journal of Toxicological Sciences
Koji Sato, Motoyuki Iemitsu
Sex steroid hormones are secreted mainly by the ovary and testis and regulate diverse physiological processes in target tissues. Recent studies have shown that sex steroidogenesis-related mRNA and protein expressions, such as for 17β-hydroxysteroid dehydrogenase (HSD), 3β-HSD, 5α-reductase and aromatase cytochrome P-450 (P450arom) enzymes, are detected in the skeletal muscle, while testosterone, estradiol, and 5α-dihydrotestosterone (DHT) were locally synthesized in skeletal muscle from dehydroepiandrosterone (DHEA)...
January 2015: Journal of Steroid Biochemistry and Molecular Biology
K Sato, S Fujita, M Iemitsu
Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg)...
September 2014: Journal of Steroid Biochemistry and Molecular Biology
Koji Sato, Motoyuki Iemitsu, Kenji Matsutani, Toshiyuki Kurihara, Takafumi Hamaoka, Satoshi Fujita
Skeletal muscle can synthesize testosterone and 5α-dihydrotestosterone (DHT) from dehydroepiandrosterone (DHEA) via steroidogenic enzymes in vitro, but hormone levels and steroidogenic enzyme expression decline with aging. Resistance exercise has been shown to increase in plasma sex steroid hormone levels. However, it remains unclear whether resistance training can restore impaired steroidogenic enzyme expressions in older individuals. Six young and 13 older men were recruited, and muscle biopsies were taken from the vastus lateralis at basal state...
April 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Katsutoshi Tokushige, Etsuko Hashimoto, Kazuhisa Kodama, Maki Tobari, Noriko Matsushita, Tomomi Kogiso, Makiko Taniai, Nobuyuki Torii, Keiko Shiratori, Yasuhiro Nishizaki, Takushi Ohga, Yoshiaki Ohashi, Takaya Sato
BACKGROUND: Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. METHODS: (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups...
December 2013: Journal of Gastroenterology
Koji Sato, Motoyuki Iemitsu, Katsuji Aizawa, Noboru Mesaki, Ryuichi Ajisaka, Satoshi Fujita
BACKGROUND: Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats. METHODS: After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group)...
2012: Nutrition & Metabolism
Jong-Hoon Park, Katsuji Aizawa, Motoyuki Iemitsu, Koji Sato, Takayuki Akimoto, Umon Agata, Seiji Maeda, Ikuko Ezawa, Naomi Omi
It is not known whether local androgen metabolism is involved in the mechanisms underlying the dehydroepiandrosterone (DHEA) administration-induced improvement of bone mineral density (BMD) in an estrogen-deficiency state. The aim of the present study was to clarify whether DHEA administration would improve local androgen metabolism and BMD in cancellous site of tibia of ovariectomized (OVX) rats. Twenty-two female rats, 6 weeks old, were randomized into three groups: sham-operated rats, OVX control rats, and OVX rats that received DHEA treatment...
August 2011: Calcified Tissue International
Koji Sato, Motoyuki Iemitsu, Katsuji Aizawa, Noboru Mesaki, Satoshi Fujita
This study was undertaken to assess the effects of dehydroepiandrosterone (DHEA) administration and exercise training on muscular DHEA and 5α-dihydrotestosterone (DHT) levels and hyperglycemia in diet-induced obese and hyperglycemic rats. After 14 wk of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of three 6-wk regimens: control, DHEA treatment, or exercise training (running at 25 m/min for 1 h, 5 days/wk; n = 10 each group). Results indicate that either 6 wk of DHEA treatment or exercise training significantly attenuated serum insulin and fasting glucose levels compared with the control group...
August 2011: American Journal of Physiology. Endocrinology and Metabolism
Katsuji Aizawa, Motoyuki Iemitsu, Seiji Maeda, Takeshi Otsuki, Koji Sato, Takashi Ushida, Noboru Mesaki, Takayuki Akimoto
Androgens, such as testosterone, play important roles in regulation of diverse physiological process of target tissues. Recently, we reported that steroidogenic enzymes exist in skeletal muscle and regulate local production of testosterone in response to exercise. Testosterone is transformed into a bioactive androgen metabolite, dihydrotestosterone (DHT) by 5alpha-reductase. However, it is unclear whether exercise stimulates local bioactive androgen metabolism in the skeletal muscle in both sexes. In the present study, we examined sex differences in the levels of dehydroepiandrosterone (DHEA), free testosterone, DHT, and steroidogenesis-related enzymes 5alpha-reductase and androgen receptor (AR) in rat's skeletal muscle before and after a single bout of exercise...
March 2010: Steroids
K Sato, M Iemitsu, K Aizawa, R Ajisaka
AIM: Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5alpha-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC zeta/lambda)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. METHODS: Using streptozotocin (STZ)-induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4-regulated signalling pathway...
November 2009: Acta Physiologica
Toshiyuki Yasui, Hirokazu Uemura, Minoru Irahara, Makoto Arai, Noriko Kojimahara, Ryugo Okabe, Yasutomo Ishii, Shin-Ichi Tashiro, Hiroshi Sato
BACKGROUND: The associations of endogenous estrogen with lipid profiles and insulin resistance were conflicting in both men and women. We determined the associations of serum estradiol level and free estradiol index (FEI) with lipid profiles and insulin resistance in aged Japanese men and women. METHODS: One hundred seventy-four men and 208 postmenopausal women aged from 50 to 85 y were included in this study. Lipid profiles, fasting glucose and insulin as well as estradiol, testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and sex hormone-binding globulin (SHBG) in serum were measured...
December 2008: Clinica Chimica Acta; International Journal of Clinical Chemistry
Tomohiro Nishimura, Yoshiaki Seki, Kazuko Sato, Takuya Chishu, Noriko Kose, Tetsuya Terasaki, Young-Sook Kang, Yoshimichi Sai, Emi Nakashima
AZT (3'-azido-3'-deoxythymidine; zidovudine), which is used for the prevention of mother-to-child transmission of HIV-1, is transplacentally transferred to the fetus across the blood-placenta barrier, which is composed of syncytiotrophoblasts. We recently showed that apical uptake of AZT by syncytiotrophoblasts is mediated by saturable transport system(s) in the TR-TBT 18d-1 cell line, and the cellular accumulation of AZT was increased in the presence of dehydroepiandrosterone sulfate (DHEAS). Here, we aimed to clarify the mechanism of this effect of DHEAS...
October 2008: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Koji Sato, Motoyuki Iemitsu, Katsuji Aizawa, Ryuichi Ajisaka
Circulating dehydroepiandrosterone (DHEA) is converted to testosterone or estrogen in the target tissues. Recently, we demonstrated that skeletal muscles are capable of locally synthesizing circulating DHEA to testosterone and estrogen. Furthermore, testosterone is converted to 5alpha-dihydrotestosterone (DHT) by 5alpha-reductase and exerts biophysiological actions through binding to androgen receptors. However, it remains unclear whether skeletal muscle can synthesize DHT from testosterone and/or DHEA and whether these hormones affect glucose metabolism-related signaling pathway in skeletal muscles...
May 2008: American Journal of Physiology. Endocrinology and Metabolism
H Sato, H Iwata, T Hayashi, K Kimura, T Kuwayama, Y Monji
The progression of the nuclear maturation of oocytes is a useful marker for the estimation of the subsequent developmental competence of oocytes. In this study, we examined the effect of energy substrates in an in vitro maturation medium on the progression of the nuclear maturation of oocytes. In experiment 1, the supplementation of the maturation medium with 0, 5 and 10 mM of glucose lead to increase in the total cell number of the blastocysts. In experiments 2 and 3, the maturation phase was divided into two stages (germinal vesicle (GV) stage: 0-20 h and nuclear maturation stage: 20-44 h), and the effects of glucose or pyruvate added at each stage on the kinetics of nuclear maturation were examined...
June 2007: Animal Reproduction Science
Sachin A Gupte, Kai-Xun Li, Takao Okada, Koichi Sato, Masahiko Oka
Cytosolic reducing cofactors, such as NADPH and NADH, are thought to regulate vascular smooth muscle ion channel activity and vascular tone. In this study, the effects of pentose phosphate pathway (PPP) inhibitors, 6-aminonicotinamide (6-AN), epiandrosterone (EPI), and dehydroepiandrosterone (DHEA), on vascular tone were studied in isolated perfused lungs and pulmonary artery (PA) and aortic rings from rats. In addition, effects of 6-AN on voltage-gated K(+) (K(v)) current in PA smooth muscle cells (SMCs) were also examined...
April 2002: Journal of Pharmacology and Experimental Therapeutics
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