Current Opinion in Endocrine and Metabolic Research最新文献

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.

As energy depots in many circumstances have been limited during evolution, it is necessary to prioritize how to manage energy resources. In this review we summarize data from the last 15 years indicating that osteoblast-lineage cells are regulators of whole-body energy metabolism and fat mass. We focus mainly on three factors, osteocalcin, lipocalin-2 and sclerostin, that are released by osteoblast-lineage cells and proposed to exert endocrine effects on metabolism. In addition, we present a hypothesis on why osteoblast-lineage cells during evolution have developed a function to regulate metabolism and fat mass. We propose that osteoblast-lineage cells through the osteocyte network in bone are sensors of gravitational forces induced by body mass and gravity on land-living species. By sensing the body weight, the osteoblastlineage cells may then feed-back this information on the whole-body nutritional status via osteoblast-derived endocrine factors or via the nervous system to regulate energy metabolism and fat mass.

There is increasing evidence from animal models that bone, in addition to its traditional function of providing structural support for the organism, has a rich network of interactions with multiple other tissues. This perspective focuses on evidence from human studies demonstrating that bone is an endocrine organ regulating energy metabolism, with the specific examples being osteocalcin, lipocalin 2, RANKL, and sclerostin. Conversely, animal studies have also demonstrated that a key hormone regulating energy metabolism, leptin, regulates bone metabolism via the sympathetic nervous system. Studies in humans have established a role for the sympathetic nervous system in regulating bone turnover; indeed, the potential therapeutic benefit of targeting this pathway in humans to prevent postmenopausal bone loss is currently being evaluated.

Depression and anxiety are amongst the most prevalent and disabling conditions worldwide, imposing significant burden to individuals, families, and their communities. It is now known that both conditions affect females more often than males, and that some can be particularly more vulnerable to symptoms (new, recurrent) during reproductive-related windows of vulnerability, including the menopause transition and early postmenopausal years.

As estrogen exerts neuro-modulatory effects on mood, cognition, and behaviour through monoaminergic systems (e.g., 5-HT, NE), rapid fluctuations of estradiol (E2) levels seem to be associated with heightened risk for/emergency of anxiety and depression during midlife years, along with other menopause-associated complaints such as vasomotor symptoms and sleep disturbances.

Psychopharmacologic and behavioural interventions remain the first-line treatment for depression and anxiety across the life span; however, estrogen-based therapies, particularly transdermal estradiol, should be considered as part of the treatment armamentarium for symptomatic, midlife women.