Current Opinion in Endocrine and Metabolic Research最新文献

The primary cilium is a sensory and signaling organelle present on most pancreatic islet endocrine cells, where it receives and interprets a wide range of intra-islet chemical cues, including hormones, peptides, and neurotransmitters. The ciliary membrane possesses a molecular composition distinct from the plasma membrane, with enrichment of signaling mediators including G protein-coupled receptors (GPCRs), tyrosine kinase family receptors, membrane transporters, and others. When activated, these membrane proteins interact with ion channels and adenylyl cyclases to trigger local Ca²⁺ and cyclic adenosine monophosphate (cAMP) activity and transmit signals to the cell body. Here we review evidence supporting the emerging model in which primary cilia on pancreatic islet cells play a central role in the intra-islet communication network and discuss how changes in cilia-mediated paracrine function in islet cells might lead to diabetes.

Thyroid cancer is the most common endocrine malignancy and is also one of the most rapidly increasing cancers worldwide. Although most patients have an excellent prognosis, a significant portion of patients experience disease relapse and metastatic progression. Treatment options for these patients remain inadequate as traditional chemotherapy has limited efficacy, and aggressive disease frequently acquires resistance to radioactive iodine. Because the majority of thyroid cancer mortality is caused by metastatic disease, there is an urgent need to elucidate the mechanisms of thyroid cancer migration and metastasis. While the mechanisms behind thyroid cancer metastasis remains in its infancy, remarkable advancements in genomics, traditional 2-dimensional cell culture, murine models, and 3-dimensional cultures have yielded new insight. This review outlines methodological approaches that can be used to investigate thyroid cancer migration and metastases and in doing so will highlight a number of recent findings that have utilized these approaches.

This review intends to bridge the gap between our knowledge of steroid hormone regulation of motile cilia and the potential involvement of the primary cilium, focusing on female reproductive tract functions. The review emphasizes hormonal regulation of the motile and primary cilia in the oviduct and uterus. Steroid hormones, including estrogen, progesterone, and testosterone, act through their cognate receptors to regulate the development and biological function of the reproductive tracts. These hormones modulate motile ciliary beating and, in some cases, primary cilia function. Dysfunction of motile or primary cilia due to genetic anomalies, hormonal imbalances, or loss of steroid hormone receptors impairs mammalian fertility. However, further research on hormonal modulation of ciliary function, especially in the primary cilium, and its signaling cascades will provide insights into the pathogenesis of mammalian infertility and the development of contraceptives or infertility treatments targeting primary and/or motile cilia.

Sodium iodide symporter (NIS)-mediated radioiodine accumulation in thyroid cancer cells is the cornerstone of radioiodine therapy for differentiated thyroid cancer. A recurring limitation of radioiodine therapy is the development of radioiodine-refractory metastatic thyroid cancer. Thyroid cancer cell dedifferentiation is the major cause of loss of radioiodine accumulation, resulting in a decreased NIS plasma membrane expression involving a plethora of transcriptional, post-transcriptional, and post-translational mechanisms. Immunohistochemical analysis revealed that most differentiated thyroid tumors preserve NIS protein expression, but NIS is often retained intracellularly, suggesting the presence of post-translational mechanisms that repress NIS plasma membrane expression. This review aims to discuss the current knowledge regarding the post-translational mechanisms that regulate NIS trafficking to the plasma membrane under physiological and pathological conditions. A thorough understanding of the molecular mechanisms underlying NIS expression at the plasma membrane would have multiple implications for radioiodine therapy, a pursuit that could uncover novel therapeutic interventions for radioiodine-refractory thyroid tumors.

It has been known for decades that bone stores high concentrations of citrate, a pivotal TCA cycle intermediate, but surprisingly little attention has been paid to explaining this curious phenomenon. Recent studies linking mutations in the sodium-citrate co-transporter (SLC13A5) to a rare neonatal epilepsy have sparked renewed interest in the study of the mechanisms controlling citrate homeostasis and mineral citrate deposition as all affected children display tooth hypomineralization. Studies from our lab using metabolic flux analysis indicate that SLC13A5 is at the center of a specialized metabolic pathway in bone, which finetunes the uptake of extracellular citrate and endogenous production in the mitochondria enabling the osteoblast to deposit citrate during cycles of bone mineralization. Loss of function of this pathway impacts circulating citrate levels and compromises bone mineral structure. These findings implicate SLC13A5 as a gatekeeper for global citrate homeostasis and is required for normal biomechanical physiological functions of bone.

Hypoxia-inducible factor (HIF) signaling activation in osteoblast lineage cells increases bone mass, likely through the combined actions of multiple key downstream effectors. These include the potent angiogenesis stimulator vascular endothelial growth factor (VEGF), which mediates coupled osteo-angiogenic responses in bone, among other non-cell-autonomous contributors. Additionally, local HIF activation in bone cells cell-intrinsically triggers increased glycolysis, which is associated with strongly enhanced osteoblastic glucose consumption. Strikingly, besides its local impact on bone mass, this boosting of cellular metabolism in the osteolineage has been linked to increased overall glucose uptake by the skeleton and concomitant effects on systemic glucose homeostasis. This review summarizes the cell-autonomous and non-cell-autonomous roles of the hypoxia signaling pathway in osteoblast lineage cells on bone physiology and the parallel systemic impact observed upon activation of the pathway in bone. New potential mechanisms extending the control of global energy metabolism by the skeleton will be discussed in light of the current evidence.

This chapter aims to review historical perspective as well as detail recent progress in neoadjuvant systemic therapy prior to surgery for advanced thyroid cancer.

Thyroid cancer is a rare cancer in the pediatric population, but incidences are rising. Thyroid tumors in children have a unique set of clinical, pathological and molecular features, and compared to adults often present with more invasive and metastatic disease. The genetic and molecular features of pediatric and adult tumors share many similar characteristics, but the prevalence of gene fusions is much higher in pediatric patients where these fusions confer greater risk for invasive and metastatic disease. Here we summarize the molecular features of pediatric papillary thyroid cancers and how these characteristics may help to guide clinical management of patients with the disease.