Current Opinion in Endocrine and Metabolic Research最新文献

Ciliary dysfunction causes a large group of developmental and degenerative human diseases known as ciliopathies. These diseases reflect the critical roles that cilia play in sensing the environment and in force generation for motility. Sensory functions include our senses of vision and olfaction. In addition, primary and motile cilia throughout our body monitor the environment allowing cells to coordinate their biology with the cells around them. This coordination is critical to organ development and maintenance, and ciliary dysfunction causes diverse structural birth defects and degenerative diseases. Deficiencies in motility lead to various health issues: lung diseases arise from impaired mucociliary clearance; male infertility results from compromised sperm motility and their inability to traverse the efferent ducts effectively; and disruptions in the left-right axis stem from nodal cilia's failure to establish accurate left-right cues.

Parathyroid tumors affect less than 0.5% of the general population. They commonly manifest as benign parathyroid adenoma (PA) in about 98% of cases, as atypical parathyroid adenoma (aPA) in 1.2%–1.3% of cases, or as malignant parathyroid carcinoma (PC) in less than 1% of patients. Over 90% of cases present as a sporadic disease, caused by somatic mutations occurred in a single parathyroid chief cell, leading to the development of a single-gland neoplasm. In less than 10% of cases, parathyroid tumors occur as a part of congenital non-syndromic or syndromic endocrine disorders, caused by a germline autosomal dominant mutation inherited by one parent, independently by sex, or, in extremely rare cases, by a de novo mutation occurred during the embryo development.

Non-sensory neurons in the mammalian brain possess a primary cilium. Neuronal cilia act as antenna and receive inputs from the extracellular environment to modulate developmental pathways and neuronal activity. These functions require ciliary enrichment of specific proteins, such as G protein-coupled receptors (GPCRs). Although most neurons possess only one cilium, gonadotropin-releasing hormone (GnRH) neurons extend multiple primary cilia. GnRH neurons are central effectors of reproductive function and cilia on GnRH neurons are enriched for the kisspeptin receptor, a GPCR required for sexual maturation and reproductive function. Here, we provide a brief background on reproduction and primary cilia, discuss what is known about primary cilia on GnRH neurons, and present approaches for further elucidating the roles of cilia on GnRH neurons.

The epithelial cells lining the lumen of the tubular system in the kidney are exposed to a highly dynamic microenvironment, owing to the fluid flow of the pro-urine through this system. Renal flow sensing has been linked to various processes in the kidney, including electrolyte reabsorption. An important mediator of renal flow sensing is the primary cilium, which is found on almost all tubular epithelial cells. In this review, we describe the reported effects of fluid flow on electrolyte transport in the different segments of the nephron and whether these effects are dependent on the primary cilium. Collectively, these studies highlight the stimulatory effect of fluid flow on electrolyte reabsorption, with a variable degree of dependency on the primary cilium.

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.