Dr. Koji Suzuki and colleague report in the March issue an extremely rare case of metastatic lung adenocarcinoma within a gonadotroph pituitary neuroendocrine tumor (PitNET), representing a considerably expeditious progression of a variety of neurological symptoms. This excellent report provides us with invaluable insight into diagnosis and therapeutics for coexisting primary and metastatic tumors in pituitary gland.
As well known, endocrine organs including pituitary gland, adrenal gland and pancreatic islet of Langerhans et cetera consist of heterogenous cells, and pathophysiological interplay among hormone-producing cells and non-hormone-producing cells within tissue is crucial, at least in part, for molecular basis of a variety of endocrine diseases. In the February issue, Dr. Ryusaku Matsumoto and Takuya Yamamoto provide a comprehensive, fascinating review article focusing on the update of single-cell and spatial transcriptomics in endocrine research. Our editorial team has a firm belief that this review is a must-read for all dedicating clinicians and scientists on endocrinology.
It is widely recognized that some cases of immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) result in life-threatening consequences including adrenal crisis and fatal diabetic ketoacidosis. In this issue, Dr. Tomoko Kobayashi and colleague contribute an insightful and well-organized review article on promising biomarkers to predict the onset of endocrine irAEs, particularly underscoring the mechanism-based management strategies and future prospect for pituitary and thyroid irAEs.
It is well known that both Ca2+ and cAMP play critical roles in ACTH-driven cortisol production by adrenal fasciculate cells. However, the division of role for Ca2+ and cAMP in this paradigm still remains obscure. In the December Issue, Dr. Masahiko Kutsukake and colleague elegantly unraveled such a long-standing enigma via sophisticated cellular experiments, demonstrating that cortisol production under steady state is preferentially mediated by Ca2+, but cAMP also participates under stressful conditions where ACTH demand is increased to adapt exaggerated stress.
As well known, immune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events in the thyroid gland (thyroid irAEs). Dr. Ichiro Yamauchi and colleague conducted an elaborate retrospective cohort study demonstrating that patients with rapid-onset severe thyrotoxicosis as well as with positive TgAbs titers were highly likely to develop subsequent hypothyroidism. This study provides us with a message that expeditious replacement of levothyroxine is a crucial precaution against severely hypothyroid state.
Complexity in action-specific resistance and hypersensitivity of hormones has long been recognized throughout the body. In particular, however, underlying molecular mechanisms of selective insulin resistance in liver are not yet fully elucidated. In the September issue, Dr. Takumi Kitamoto and Professor Domenico Accili provide an elegant, comprehensive review article on such a longstanding enigma.
Unravelling the complexed molecular pathophysiology of diabetic nephropathy is no doubt a key to establish cutting-edge therapeutics against end stage renal diseases (ESRDs) and cardiovascular events. In this issue, Dr. Keiichiro Matoba contributes an elegant article particularly focusing on the promising potential of Rho-associated, coiled-coil-containing protein kinase (ROCK) for the treatment of diabetic nephropathy. ROCK signaling is known to exaggerate in the diabetic kidney. Of note, ROCK1 blunts AMPK signaling, thereby hampering mitochondrial function, while ROCK2 attenuates PPARα signaling, resulting in the decrease in fatty acid oxidation. Collectively, his work does shed light on the novel approach toward the diabetic nephropathy via kidney-specific inhibition of ROCK signaling.
Age-related testosterone decline, also known as late-onset hypogonadism (LOH), is tightly linked with a wide variety of aging-related pathophysiology including sarcopenia, coronary arterial disease, arteriosclerosis, obesity disease, type 2 diabetes mellitus, mental health disorders and cognitive impairment. In this issue, Professor Hisamitsu Ide timely contributes an insightful and well-organized review article on testosterone with a specific view point of clinical and molecular endocrinology, underscoring the huge impact of testosterone on maintenance of male health in the super-aging society.
Immune-related adverse effects observed in a variety of endocrine organs caused by immune checkpoint inhibitors (ICIs) afresh underscore the impact of onco-immuno-endocrinology on the pathophysiology and pathogenesis of paraneoplastic endocrine syndrome. In this issue, Professor Yutaka Takahashi contributes a terrific, well-organized article on the recent research progress particularly in the category of paraneoplastic autoimmune hypophysitis including anti-PIT-1 hypophysitis, isolated ACTH deficiency and ICI-related hypophysitis.
Reproductive endocrinology provides us with a lot of tips in a various area of medical science. In this issue, Dr. Tamura and colleague contribute an insightful review article focusing on glucose and lipid metabolism in human endometrial stromal cells during the course of decidualization. To effectively supply energy for embryo, human endometrial stromal cells aggressively ingest fuel via GLUT1 and VLDL receptor under the transcriptional control and epigenetic modification involved in C/EBP beta, p300 and WT1. Such a fashion would be reminiscent, at least in part, of fuel metabolism commonly seen in cancer cells. It is also anticipated that energy metabolism-based unique approach in this article opens a fresh avenue for cutting edge medicine and therapeutics on incomplete implantation or infertility.
As well known, comparative endocrinology has long provided deep insight into pathophysiology and molecular basis of a variety of human endocrinologic diseases. In this issue, by use of a small fish model, Dr. Yoshitaka Oka contributes an extensive, well-organized article on the recent research progress in neuroendocrine regulation of reproduction by GnRH neurons, providing us with an invaluable perspective for cutting-edge area of reproductive endocrinology in humans.
It is well recognized that a line of symptoms of neurohypophyseal diabetes insipidus (NDI), also known as arginine vasopressin (AVP) deficiency, are masked under the condition of adrenal insufficiency. However, molecular mechanisms whereby polyuria manifests after the administration of glucocorticoids in patients with masked NDI have not been fully elucidated. Kurimoto J and colleague elegantly solved this long-lasting enigma via comprehensive analyses including patients with masked NDI as well as murine model of familial NDI. They provide a convincing proof that mineralcorticoids directly attenuate the expression of aquaporin-2 in the apical membrane of collecting duct, thereby leading to the increase in urine volume in patients with NDI.
To date, familial partial lipodystrophy (FPLD) has been known to consist of seven types, and FPLD type 3 is a rare autosomal dominant genetic disorder caused by mutations of peroxisome proliferator-activated receptor γ gene. In this issue, Dr. Iizaka and colleague report the first pedigree of FPLD 3 in Japanese exemplifying prolonged insulin resistant diabetes mellitus, liver steatosis and hypertriglyceridemia with a relatively low degree of BMI and percentage of body fat. For all endocrinologists, attention should be paid to avoid overlooking lipodystrophy syndromes.
Molecular research on agonists / antagonists / inverse agonists in a variety of G-protein coupled receptors (GPCRs) has long attracted robust attention of endocrinologists. In this issue, Dr. Nagayama and Dr. Nishihara contributes an encyclopedic, well-organized article on the update of antagonists / inverse agonists research around the thyrotropin receptor (TSHR), providing us with promising therapeutic potential for Graves’ hyperthyroidism, non-autoimmune hyperthyroidism, thyroid cancer and resistance to thyroid hormone.
It has long been recognized that uncontrolled high blood pressure, dysmetabolism of glucose and lipids, and sustained inflammation and fibrosis are involved in the pathophysiology and progression of diabetic kidney disease (DKD) in an extremely complexed manner. It is therefore exactly a herculean issue to accurately identify patients with higher risks than we would imagine for end-stage renal diseases (ESRDs). In the October issue, Dr. Xu Ning and colleague provide an attractive review article focusing on potentials of mesenchymal stem cells (MSCs) for the treatment of such an intractable medical condition.
Epigenome-based drugs such as inhibitors against DNA methyltransferases (DNMTs) and histone deacetylase (HDACs) have long been employed for the treatment of a variety of malignancy and pre-cancer status. In this issue, Dr. Rie Hagiwara and colleague provide a convincing data set of in vitro experiments demonstrating a selective HDAC6 inhibitor, tubastatin A substantially suppresses the growth of as well as the ACTH secretion from a murine corticotroph cell line, AtT-20. The present study may open a fresh avenue for brand-new therapeutics in humans on pituitary neuroendocrine tumors including Cushing’s disease.
Science and clinics on phosphate homeostasis are no doubt an authentic, royal road to endocrinology. As most of readers of Endocrine Journal well recognize, basic scientists and endocrinologists in Japan have made a huge contribution to the molecular medicine on fibroblast growth factor 23 (FGF 23) in this academic field. To STATE-OF-THE-ART REVIEW IN ENDOCRINOLOGY in this issue, Dr. Michigami contributes an extensive, well-organized article on the recent research progress in phosphate homeostasis and related disorders with a particular emphasis on FGF 23, providing us with an invaluable perspective for cutting-edge area of bone-mineral endocrinology.
Dynamic remodeling of adipose tissue plays a critical role in the pathophysiology of obesity disease. In this article, Dr. Yutaka Hasegawa elegantly updates the research on the molecular mechanism whereby adipocytes interact with non-adipocytes during the course of adipose dysfunction and fibrosis in obesity. This review does provide us with invaluable perspective for endocrinology-based obesity science.
It has been highlighted that postprandial hyperinsulinemia-associated hypoglycemia sometimes happens in patients with morbid obesity after metabolic surgeries. In the present study, Dr. Yukako Yamamoto and her colleague provide a line of convincing data demonstrating that a 75 g glucose- and high fat-containing cookie meal test is useful in severely obese subjects to precisely evaluate glucose intolerance and postprandial dyslipidemia without occurrence of hyperinsulinemia-associated hypoglycemia. The cookie meal test may open a fresh avenue to conveniently monitor fuel homeostasis in the course of multidisciplinary therapies for obese-diabetic patients.
A variety of factors including dysregulation of renin-angiotensin-aldosterone system in both systemically and locally are well known to affect the progression of diabetic nephropathy (DN).To our surprise, however, the possible association between the plasma renin activity (PRA) and renal outcomes in patients with DN still remains obscure. In the present article, Dr. Kazuyoshi Kuma and colleague elegantly addressed such a unsolved question in a 2 year-prospective study, highlighting that low in PRA is an independent risk for the progression of DN in a Japanese cohort.