Ghrelin produced in the stomach promotes food intake and GH secretion, and acts as an anabolic peptide during starvation. Ghrelin binds to the growth hormone secretagogue receptor, a G protein-coupled receptor (GPCR), whose high-resolution complex structures have been determined in the apo state and when bound to an antagonist. Anamorelin, a low-molecular-weight ghrelin agonist, has been launched in Japan for the treatment of cancer cachexia, and its therapeutic potential has attracted attention due to the various biological activities of ghrelin. In 2019, liver-expressed antimicrobial peptide (LEAP2), initially discovered as an antimicrobial peptide produced in the liver, was identified to be upregulated in the stomach of diet-induced obese mice after vertical sleeve gastrectomy. LEAP2 binds to the GHSR and antagonizes ghrelin’s activities. The serum concentrations of human LEAP2 are positively correlated with body mass index, body fat accumulation, and fasting serum concentrations of glucose and triglyceride. Serum LEAP2 elevated and ghrelin reduced in obesity. Ghrelin and LEAP2 regulate body weight, food intake, and GH and blood glucose concentrations, and other physiological phenomena through their interactions with the same receptor, GHSR.
Recommendation from the Editor in Chief
There are examples
where distinct two peptide ligands respectively act as
an agonist and antagonist on the same receptor. To my knowledge, the
best-known one is related with the story that alpha-MSH and agouti-related
peptide (AgRP) act on the melanocrtin-4 receptor (MC4R) as an agonist and
antagonist, thereby minutely regulating appetite and body weight. In this
issue, Dr. Katsuya Sakai and Professor Masamitsu Nakazato, a world-renowned
physician scientist on research of orexigenic hormone ghrelin, provide us with
well-organized, fabulous review article focusing on the dynamic interaction
between ghrelin and LEAP-2 (liver-expressed antimicrobial peptide 2) in terms
of stomach-liver axis-driven appetite control. Indeed, ghrelin and LEAP-2
respectively act as an agonist and antagonist on the same receptor, GHSR
(growth hormone secretagogue receptor). Our editorial team has
a firm belief that all readers are surely motivated by the real deal of
authentic endocrinology and cutting-edge medicine on GPCR signal transduction
in this article.
Androgen is widely acknowledged to regulate skeletal muscle mass. However, the specific mechanism driving muscle atrophy resulting from androgen deficiency remains elusive. Systemic androgen receptor knockout (ARKO) mice exhibit reduction in both muscle strength and muscle mass while skeletal muscle fiber specific ARKO mice have decreased muscle strength without affecting skeletal muscle mass in the limbs. Therefore, androgens may indirectly regulate skeletal muscle mass through effects on non-myofibers. Considering this, our investigation focused on blood fluid factors that might play a role in the regulation of skeletal muscle mass under the influence of androgens. Using a male mouse model of sham, orchidectomy and DHT replacement, mass spectrometry for serum samples of each group identified epidermal growth factor receptor (EGFR) as a candidate protein involving the regulation of skeletal muscle mass affected by androgens. Egfr expression in both liver and epididymal white adipose tissue correlated with androgen levels. Furthermore, Egfr expression in these tissues was predominantly elevated in male compared to female mice. Interestingly, male mice exhibited significantly elevated serum EGFR concentrations compared to their female counterparts, suggesting a connection with androgen levels. Treatment of EGFR to C2C12 cells promoted phosphorylation of AKT and its downstream S6K, and enhanced the protein synthesis in vitro. Furthermore, the administration of EGFR to female mice revealed a potential role in promoting an increase in skeletal muscle mass. These findings collectively enhance our understanding of the complex interplay among androgens, EGFR, and the regulation of skeletal muscle mass.
Recommendation from the Editor in Chief
Reflecting an expeditious increase in elder patients with sarcopenia notably in industrialized countries, endocrinologic research on molecular basis of muscle mass and strength has attracted great attention in both academic and clinical fields. In this issue, Dr. Tomoya Onishi, Professor Yuuki Imai and colleague provide fresh insight into unexpected interplay between androgens and epidermal growth factor receptor (EGFR) EGFR in the molecular pathophysiology of shrinkage of muscle mass. This excellent article provides all endocrinologists with updated viewpoint of sarcopenia science.
This study aimed to focus on the role of radiologists in the diagnosis and management of adrenal lesions, particularly primary aldosteronism (PA) and secondary hypertension. As hypertension affects more than one-third of the population in Japan, identifying secondary causes such as PA and adrenal lesions is crucial. Establishing a radiological differential diagnosis of adrenal lesions using advanced imaging techniques, such as computed tomography and magnetic resonance imaging, is crucial. Knowledge of the imaging findings of various benign and malignant adrenal lesions, such as adrenocortical adenomas, cortisol-producing lesions, pheochromocytomas, adrenocortical carcinoma, malignant lymphoma, and metastatic tumors, is necessary. Adrenal venous sampling (AVS) plays a crucial role in accurately localizing aldosterone hypersecretion in PA, especially when imaging fails to provide a clear diagnosis. This paper details the technical aspects of AVS, emphasizing catheterization techniques, anatomical considerations, and the importance of preprocedural imaging for successful sampling. Furthermore, we explore segmental adrenal venous sampling (SAVS), a more refined technique that samples specific adrenal tributary veins, offering enhanced diagnostic accuracy, particularly for microadenomas or challenging cases that may be missed with conventional AVS. The methodology for performing SAVS, along with the interpretation criteria for successful sampling and lateralization, is also outlined. Furthermore, radiologists have initiated treatments for unilateral PA, such as radiofrequency ablation, and play an integral role in the management of adrenal lesions. Collaborative approaches across clinical departments are required to enhance patient management in medical care involving the adrenal gland.
Recommendation from the Editor in Chief
Radiographic diagnosis and therapeutic approach are
requisite for clinics of endocrinology, especially for a series of adrenal
diseases. From the unique standpoint of proficient radiologist, Dr. Oguro and
colleague contribute a comprehensive and extensive review article focusing on
this issue with a particular emphasis on segmental adrenal venous sampling
(SAVS) and radiofrequency ablation for the treatment of unilateral primary aldosteronism
(PA), shedding light on the importance of collaborative approach toward intractable
endocrine diseases.
Almost a century has passed since Plummer reported the efficacy of short-term preoperative inorganic iodine therapy for Graves’ disease in the 1920s. Since there were concerns about the escape phenomenon and exacerbation with inorganic iodine, antithyroid drugs became the mainstay of pharmacotherapy for Graves’ disease following their development in the 1940s. With regard to long-term inorganic iodine monotherapy, Trousseau reported a case in the 1860s, and several subsequent reports suggested its efficacy. Around 1930, Thompson et al. published a number of papers and concluded that long-term inorganic iodine monotherapy was useful if limited to mild cases under careful follow-up. From Japan, in 1970, Nagataki et al. reported that, of 12 patients treated with inorganic iodine, three remained eumetabolic for more than two years. Since 2014, some reports have also been published from Japan. A summary of these recent reports is given below. The starting dose of potassium iodide is around 50 mg/day, and candidate responders have mild disease, with FT4 <2.76 ng/dL (35.5 pmol/L), a small goiter, and are female and elderly. Response rates are relatively high, at 60–80%, and the remission rate is about 40%. In cases of insufficient response, changing therapy should be considered. Inorganic iodine can be used as a possible alternative if the patient experiences adverse events with antithyroid drugs and/or prefers conservative treatments, with an understanding of their efficacy and limitations. These recent reports have been published from Japan, where iodine is sufficient, and the dose of inorganic iodine is empirical and requires further study.
Recommendation from the Editor in Chief
It has been well recognized that inorganic iodine persistently suppresses thyroid function in some cases with Graves’ disease, and can be introduced as an alternative for patients with adverse events on antithyroid drugs. However, scientific bases are not fully elucidated and still remains empirical. In this issue, Dr. Natsuko Watanabe, an editorial board member of Endocrine Journal (EJ), contributes a well-organized, insightful narrative review focusing on this issue. The editorial team of EJ has a firm belief that all readers will be fascinated by an implicative “historical tale” around the relation between iodine and thyroid.
Cushing’s disease is associated with increased morbidity and mortality. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained mean urinary free cortisol (mUFC) normalization in Cushing’s disease patients in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734). Here, we evaluate the efficacy and safety of osilodrostat in Cushing’s disease in patients of Asian origin compared with patients of non-Asian origin. Pooled data from LINC 3 and LINC 4 were analyzed. Outcomes were evaluated separately for Asian and non-Asian patients. For the analysis, 210 patients were included; 56 (27%) were of Asian origin. Median (minimum–maximum) osilodrostat dose was 3.8 (1–25) and 7.3 (1–47) mg/day in Asian and non-Asian patients, respectively. mUFC control was achieved at weeks 48 and 72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients. Improvements in cardiovascular and metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life were similar in both groups. Most common adverse events (AEs) were adrenal insufficiency (44.6%) in Asian and nausea (45.5%) in non-Asian patients. AEs related to hypocortisolism and pituitary tumor enlargement occurred in more Asian (58.9% and 21.4%) than non-Asian patients (40.3% and 9.1%). Of Asian and non-Asian patients, 23.2% and 13.6%, respectively, discontinued because of AEs. Asian patients with Cushing’s disease generally required numerically lower osilodrostat doses than non-Asian patients to achieve beneficial effects. Hypocortisolism-related AEs were reported in more Asian than non-Asian patients. Together, these findings suggest that Asian patients are more sensitive to osilodrostat than non-Asian patients.
Recommendation from the Editor in Chief
Ethnicity-dependent differences in drug responsiveness have attracted
broad attention also in endocrinological science. In this issue, Dr.
Akira Shimatsu and Professor Beverly MK Biller at Massachusetts General
Hospital, an active member of international honorary editors of
Endocrine Journal, contribute an insightful original article focusing on
ethnicity-related impact of oral 11beta-hydroxylase inhibitor,
Osilodrostat between patients with Cushing’s disease of Asian and
non-Asian origin. In comparison with non-Asians, Asian patients required
apparently-lower doses of the drug to achieve clinical benefits,
whereas adverse events related with hypocortisolism were manifested in
Asians. As authors stated, this study is the first to compare the impact
of drug therapy for patients with Cushing’s disease between Asian and
non-Asian origin. Although ethnicity-dependent differences in
bioavailability of the drug would be involved, elucidation of the entire
picture is strongly anticipated.
Effects of pre- and post-pubertal dihydrotestosterone treatment on penile length in 5α-reductase type 2 deficiency
Released on J-STAGE: September 28, 2019 | Volume 66 Issue 9 Pages 837-842
Goro Sasaki, Tomohiro Ishii, Naoaki Hori, Naoko Amano, Keiko Homma, Seiji Sato, Tomonobu Hasegawa
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Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis
Released on J-STAGE: January 28, 2019 | Volume 66 Issue 1 Pages 51-63
Yaping Liang, Xiaojia Xu, Mingjuan Yin, Yan Zhang, Lingfeng Huang, Ruoling Chen, Jindong Ni
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Effects of 50 mg vildagliptin twice daily vs. 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose
Released on J-STAGE: April 29, 2017 | Volume 64 Issue 4 Pages 417-424
Hiroshi Nomoto, Kimihiko Kimachi, Hideaki Miyoshi, Hiraku Kameda, Kyu Yong Cho, Akinobu Nakamura, So Nagai, Takuma Kondo, Tatsuya Atsumi
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The effect of acute sleep deprivation on cortisol level: a systematic review and meta-analysis
Released on J-STAGE: August 08, 2024 | Volume 71 Issue 8 Pages 753-765
Yifei Chen, Wenhui Xu, Yiru Chen, Jiayu Gong, Yanyan Wu, Shutong Chen, Yuan He, Haitao Yu, Lin Xie
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The impact of testosterone in men’s health
Released on J-STAGE: July 28, 2023 | Volume 70 Issue 7 Pages 655-662
Hisamitsu Ide
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