Bone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human body, and around 85% of phosphate is present in bone as a constituent of hydroxyapatite, Ca10(PO4)6(OH)2. Because hypophosphatemia induces rickets/osteomalacia, and hyperphosphatemia results in ectopic calcification, blood phosphate (inorganic form) level must be regulated in a narrow range (2.5 mg/dL to 4.5 me/dL in adults). However, as yet it is unknown how bone senses changes in blood phosphate level, and how bone regulates the production of FGF23. Our previous data indicated that high extracellular phosphate phosphorylates FGF receptor 1 (FGFR1) in an unliganded manner, and its downstream intracellular signaling pathway regulates the expression of GALNT3. Furthermore, the post-translational modification of FGF23 protein via a gene product of GALNT3 is the main regulatory mechanism of enhanced FGF23 production due to high dietary phosphate. Therefore, our research group proposes that FGFR1 works as a phosphate-sensing receptor at least in the regulation of FGF23 production and blood phosphate level, and phosphate behaves as a first messenger. Phosphate is involved in various effects, such as stimulation of parathyroid hormone (PTH) synthesis, vascular calcification, and renal dysfunction. Several of these responses to phosphate are considered as phosphate toxicity. However, it is not clear whether FGFR1 is involved in these responses to phosphate. The elucidation of phosphate-sensing mechanisms may lead to the identification of treatment strategies for patients with abnormal phosphate metabolism.
Fibroblast growth factor 23 (FGF23) plays a critical role in regulating circulating phosphate level. To date, however, mechanisms whereby bone senses the change of blood phosphate level and regulates the production of FGF23 have been poorly elucidated. In this issue, Dr. Yuichi Takashi contributes an insightful review article focusing on such long-lasting enigmas. Our editorial team is sure that readers will be fascinated by the profound world of phosphate homeostasis via unique endocrine systems.
Collision tumors involving the metastasis of malignant neoplasms to pituitary neuroendocrine tumors (PitNETs) are extremely rare. We herein report a case involving a patient with lung adenocarcinoma metastasis within a PitNET who exhibited relatively rapid progression of neurological symptoms. A 75-year-old man who underwent tumor resection 36 and 18 years prior to presentation for bladder and colon cancer, respectively, without recurrence presented with bitemporal hemianopsia, ptosis, and diplopia of the right eye. Subsequent magnetic resonance imaging (MRI) revealed a tumor 3.2 cm in diameter that extended from the anterior pituitary gland to the suprasellar region. Gadolinium-enhanced MRI of the tumor showed heterogeneous contrast enhancement. Considering the relatively rapid progression of neurological symptoms, semi-emergency endoscopic endonasal transsphenoidal surgery was performed. Histopathological examination revealed a group of thyroid transcription factor-1- and napsin A-positive papillary proliferating cells intermingled with α-subunit- and steroidogenic factor-1-positive PitNET cells. Thus, the patient was diagnosed with lung adenocarcinoma metastasis within a gonadotroph PitNET. Genetic testing revealed the presence of an EGFR (Ex-19del) mutation, after which chemotherapy was initiated. Additional stereotactic radiotherapy was performed for the residual tumor in the sella turcica. With continued chemotherapy, good control of both the primary and metastatic tumors was noted after 24 months after surgery. Cases of malignant neoplasm metastasis within a PitNET are difficult to diagnose. In the case of a sella turcica tumor with relatively rapid progression of neurological symptoms, early surgical intervention is recommended given the possibility of a highly proliferative tumor and the need to obtain pathologic specimens.
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.
Accumulating evidence suggests that cellular heterogeneity in organs and cell-cell and tissue-tissue interactions are crucial for maintaining physical homeostasis and disease progression. Endocrine organs also exhibit cellular heterogeneity and comprise multiple cell types. For instance, the pituitary gland comprises five types of pituitary hormone-producing cells as well as non-hormone-producing supporting cells, such as fibroblasts, endothelial cells, and folliculostellate cells. However, the functional roles of the interactions between hormone-producing and non-producing cells in the pituitary gland remain incompletely understood. Over the past decade, emerging technologies such as single-cell and spatial transcriptomics have provided excellent tools for studying cellular heterogeneity and their interactions; however, the application of these technologies in endocrine research remains limited. This review provides an overview of these technologies and discusses their strengths and limitations. Additionally, we also summarize the potential future applications of single-cell and spatial transcriptomics in the study of endocrine organs and their disorders.
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.
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.
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.
In adrenal fasciculata cells stimulated by ACTH, Ca2+ and cAMP play indispensable roles as second messengers in cortisol production. However, whether their second messengers cooperatively or independently participate in steroid production remains unclear. We focused on the roles of Ca2+ and cAMP in cortisol production in bovine adrenal fasciculata cells stimulated by ACTH for a relatively short period (1 h). Incubation of the cells with 100 pM ACTH in Ca2+-containing (normal) medium for 1 h increased cortisol production without affecting cAMP content. In contrast, treatment of the cells with the peptide at a higher concentration (1 nM) significantly augmented both cortisol production and cAMP content. However, ACTH did not increase either of them in the Ca2+-free medium. ACTH rapidly increased the intracellular free Ca2+ concentration ([Ca2+]i) in the normal medium, but did not influence [Ca2+]i in the Ca2+-free medium, indicating that ACTH caused Ca2+ influx into the cells. ACTH-induced Ca2+ influx and cortisol production were suppressed by a voltage-sensitive L-type Ca2+ channel blocker but not by a T-type, N-type, or P-type Ca2+ channel blocker. In contrast, dibutyryl cAMP, a cell-permeable cAMP analog, greatly enhanced cortisol production in the normal or Ca2+-free medium and slowly caused Ca2+ influx into the cells. These results strongly suggest that Ca2+, as a second messenger, is more critical than cAMP for cortisol production. However, both second messengers jointly participate in the production in adrenal fasciculata cells stimulated by ACTH.
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.
Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials
Released on J-STAGE: June 28, 2021 | Volume 68 Issue 6 Pages 739-742
Dao-Gen Yin, Liang-Liang Ding, Hai-Rong Zhou, Mei Qiu, Xue-Yan Duan
Views: 1,485
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
Views: 1,126
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: 987
Relation between HOMA-IR and insulin sensitivity index determined by hyperinsulinemic-euglycemic clamp analysis during treatment with a sodium-glucose cotransporter 2 inhibitor
Released on J-STAGE: May 28, 2020 | Volume 67 Issue 5 Pages 501-507
Anna So, Kazuhiko Sakaguchi, Yuko Okada, Yasuko Morita, Tomoko Yamada, Hiroshi Miura, Natsu Otowa-Suematsu, Tomoaki Nakamura, Hisako Komada, Yushi Hirota, Yoshikazu Tamori, Wataru Ogawa
Views: 966
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: 593