Decidualization is a process of differentiation of human endometrial stromal cells (hESCs) accompanied by dramatic changes in cellular functions. This process is critical for embryo implantation and the establishment of pregnancy. Impairment of decidualization of hESCs leads to implantation failure, miscarriage, and unexplained infertility. The present review focuses on the metabolic changes in hESCs during decidualization. One of the changes taking place is in the glucose metabolism. Glucose uptake increases during decidualization because glucose is essential for the decidualization of hESCs. In hESCs, GLUT1 is highly expressed and involved in the increase of glucose uptake during decidualization. The up-regulation of GLUT1 is mediated by an epigenetic mechanism, which is regulated by CCAAT enhancer-binding protein β (C/EBPβ) and Wilms tumor 1 (WT1). Another metabolic change is in the lipid metabolism. Lipid accumulation in hESCs increases during decidualization. This increase is mediated by very low-density lipoprotein receptor (VLDLR). The up-regulation of VLDLR is regulated by WT1. In contrast to glucose, lipid is not essential for decidualization of hESCs. Endometrial cells have been implicated as important sources of nutrition for the embryo. hESCs may increase glucose and lipid storage so that they can supply them to the embryo during the implantation process. Taken together, decidualization is the process accompanied by metabolic changes, which may be associated with successful implantation.
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.
After the discovery of GnRH, GnRH neurons have been considered to represent the final common pathway for the neural control of reproduction. There is now compelling data in mammals that two populations of kisspeptin neurons constitute two different systems to control the episodic and surge release of GnRH/LH for the control of different aspects of reproduction, follicular development and ovulation. However, accumulating evidence indicates that kisspeptin neurons in non-mammalian species do not serve as a regulator of reproduction, and the non-mammalian species are believed to show only surge release of GnRH to trigger ovulation. Therefore, the GnRH neurons in non-mammalian species may offer simpler models for the study of their functions in neuroendocrine regulation of reproduction, especially ovulation. Our research group has taken advantage of many unique technical advantages of small fish brain for the study of anatomy and physiology of GnRH neurons, which underlie regular ovulatory cycles during the breeding season. Here, recent advances in multidisciplinary study of GnRH neurons are reviewed, with a focus on studies using small teleost fish models.
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.
The symptoms of diabetes insipidus may be masked by the concurrence of adrenal insufficiency and emerge after the administration of hydrocortisone, occasionally at high doses. To elucidate the mechanism underlying polyuria induced by the administration of high-dose corticosteroids in the deficiency of arginine vasopressin (AVP), we first examined the secretion of AVP in three patients in whom polyuria was observed only after the administration of high-dose corticosteroids. Next, we examined the effects of dexamethasone or aldosterone on water balance in wild-type and familial neurohypophyseal diabetes insipidus (FNDI) model mice. A hypertonic saline test showed that AVP secretion was partially impaired in all patients. In one patient, there were no apparent changes in AVP secretion before and after the administration of high-dose corticosteroids. In FNDI mice, unlike dexamethasone, the administration of aldosterone increased urine volumes and decreased urine osmolality. Immunohistochemical analyses showed that, after the administration of aldosterone in FNDI mice, aquaporin-2 expression was decreased in the apical membrane and increased in the basolateral membrane in the collecting duct. These changes were not observed in wild-type mice. The present data suggest that treatment with mineralocorticoids induces polyuria by reducing aquaporin-2 expression in the apical membrane of the kidney in partial AVP deficiency.
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.
Familial partial lipodystrophy (FPLD) 3 is a rare genetic disorder caused by peroxisome proliferator-activated receptor γ gene (PPARG) mutations. Most cases have been reported in Western patients. Here, we describe a first pedigree of FPLD 3 in Japanese. The proband was a 51-year-old woman. She was diagnosed with fatty liver at age 32 years, dyslipidemia at age 37 years, and diabetes mellitus at age 41 years. Her body mass index was 18.5 kg/m2, and body fat percentage was 19.2%. On physical examination, she had less subcutaneous fat in the upper limbs than in other sites. On magnetic resonance imaging, atrophy of subcutaneous adipose tissue was seen in the upper limbs and lower legs. Fasting serum C-peptide immunoreactivity was high (3.4 ng/mL), and the plasma glucose disappearance rate was low (2.07%/min) on an insulin tolerance test, both suggesting apparent insulin resistance. The serum total adiponectin level was low (2.3 μg/mL). Mild fatty liver was seen on abdominal computed tomography. On genetic analysis, a P495L mutation in PPARG was identified. The same mutation was also seen in her father, who had non-obese diabetes mellitus, and FPLD 3 was diagnosed. Modest increases in body fat and serum total adiponectin were seen with pioglitazone treatment. Attention should be paid to avoid overlooking lipodystrophy syndromes even in non-obese diabetic patients if they show features of insulin resistance.
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.
The thyrotropin receptor (TSHR) plays critical roles in thyroid growth and function and in the pathogenesis of several thyroid diseases including Graves’ hyperthyroidism and ophthalmopathy, non-autoimmune hyperthyroidism and thyroid cancer. Several low-molecular weight compounds (LMWCs) and anti-TSHR monoclonal antibodies (mAbs) with receptor antagonistic and inverse agonistic activities have been reported. The former binds to the pocket formed by the receptor transmembrane bundle, and the latter to the extracellular TSH binding site. Both are effective inhibitors of TSH/thyroid stimulating antibody-stimulated cAMP and/or hyaluronic acid production in TSHR-expressing cells. Anti-insulin-like growth factor 1 inhibitors are also found to inhibit TSHR signaling. Each agent has advantages and disadvantages; for example, mAbs have a higher affinity and longer half-life but are more costly than LMWCs. At present, mAbs appear most promising, yet the development of more efficacious LMWCs is desirable. These agents are anticipated to be efficacious not only for the above-mentioned diseases but also for resistance to thyroid hormone and have utility for thyroid cancer radionuclide scintigraphy/therapy as a new theranostic.
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.
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
Views: 680
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Released on J-STAGE: February 28, 2020 | Volume 67 Issue 2 Pages 153-160
Junichiro Irie, Emi Inagaki, Masataka Fujita, Hideaki Nakaya, Masanori Mitsuishi, Shintaro Yamaguchi, Kazuya Yamashita, Shuhei Shigaki, Takashi Ono, Hideo Yukioka, Hideyuki Okano, Yo-ichi Nabeshima, Shin-ichiro Imai, Masato Yasui, Kazuo Tsubota, Hiroshi Itoh
Views: 598
Proposed cut-off value of CA19-9 for detecting pancreatic cancer in patients with diabetes: a case-control study
Released on J-STAGE: June 27, 2018 | Volume 65 Issue 6 Pages 639-643
Mariko Murakami, Yoshio Nagai, Ayumi Tenjin, Yasushi Tanaka
Views: 349
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
Views: 320
2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition)
Released on J-STAGE: December 30, 2016 | Volume 63 Issue 12 Pages 1025-1064
Tetsurou Satoh, Osamu Isozaki, Atsushi Suzuki, Shu Wakino, Tadao Iburi, Kumiko Tsuboi, Naotetsu Kanamoto, Hajime Otani, Yasushi Furukawa, Satoshi Teramukai, Takashi Akamizu
Views: 235