Current Opinion in Endocrine and Metabolic Research最新文献

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors which secrete catecholamines, causing cardiovascular compromise. While isolated tumors and locoregional disease can be treated surgically, treatment options for metastatic disease are limited, and no targeted therapies exist. Approximately 25% of PPGL are causatively associated with germline pathogenic variants, which are known risk factors for multifocal and metastatic PPGL. Knowledge of somatic driver mutations continues to evolve. Molecular classification of PPGL has identified three genomic subtypes: Cluster 1 (pseudohypoxia), Cluster 2 (kinase signaling) and Cluster 3 (Wnt-altered). This review summaries recent studies characterizing the tumor microenvironment, genomic drivers of tumorigenesis and progression, and current research on molecular targets for novel diagnostic and therapeutic strategies in PPGL.

Metabolites in exercise have traditionally been viewed as a fuel source, waste product, or anabolic components required for exercise-induced biosynthetic processes. However, it is now recognised that metabolites and lipids may act as mediators of interorgan crosstalk to coordinate the local and systemic physiological adaptations required to meet the complex system-wide challenge of exercise. These bioactive metabolite and lipid signals have been termed metabokines and lipokines, respectively. There is emerging evidence that metabokines and lipokines contribute to the health benefits of exercise. This review highlights several of the key recent discoveries related to metabokine and lipokine signalling during exercise. The discovery of these metabokines and lipokines, and their signalling targets, may provide the basis of future therapies for human disease.

The bone marrow stroma supports hematopoiesis while replenishing osteoblasts and adipocytes. These functions rely on different stromal cell populations identified by lineage tracing, phenotypic markers and single-cell transcriptomic analysis. A marrow stromal cell subset expressing Adiponectin (Adipoq⁺) has been reported by different studies in mice. However, while there is a general agreement on the kinetics of Adipoq⁺ stromal cells during mouse growth, their ability to generate bone marrow adipocytes and to support the bone vasculature, contrasting results have been reported on their osteogenic activity.

In this work, we review available data on Adipoq⁺ stromal cells, with special focus on the experimental evidence demonstrating their osteoprogenitor function and the potential reasons for the divergence observed among different studies. Furthermore, we discuss the potential overlap of Adipoq⁺ cells with other cell populations in the context of the widely recognized adipogenic bias that characterizes many marrow stromal stem cell populations.

Medullary thyroid cancer (MTC) is a neuroendocrine malignant tumor that originates from parafollicular C-cells, producing calcitonin. Approximately 75% of cases are sporadic, while the remaining 25% are hereditary. The main molecular alteration implicated in MTC tumorigenesis, whether sporadic or hereditary, is a point mutation in the RET gene. Surgery is the initial treatment of choice, while subsequent treatments are determined based on the tumor burden and rate of progression. While in case of single metastases, low tumor burden with slow rate of progression local treatments are recommended, systemic treatments are warranted in cases with large metastatic disease and rapidly progressive conditions. Beyond multikinase inhibitors (MKIs), new highly selective compounds against RET mutation, with high efficacy and good safety profile, have been recently used in clinical trials for advanced MTC patients.

This review focuses on the details of systemic treatments with highly selective RET inhibitors for advanced and metastatic MTC.

There is a discrepancy between the distribution of melanin-concentrating hormone (MCH)-immunoreactive fibers and the mRNA expression of MCH receptors, particularly MCH₁. Furthermore, the presence of MCH₁ in the primary cilia of adjacent areas with richness of MCH-ir fibers, adds complexity to the neurochemical signaling dynamics. This intricate interplay, facilitated by volume transmission (VT) and the strategic positioning of receptors on structures like primary cilia, presents a novel perspective on neuroendocrine communication. An in-depth exploration of MCH, primary cilia, MCH₁, and VT interactions promises to uncover unprecedented insights that could enhance our understanding of their implications for health and disorders, like obesity. An exploration into the ciliary mechanisms of MCH action emerges as a promising venue for uncovering potential therapeutic targets.

The adrenergic system plays a central role in human physiology. However, it can also affect commensal bacteria via adrenergic hormones. Bacteria use adrenergic hormones as xenosiderophore for iron supply, modulators of biofilm formation, quorum-sensing autoinducers regulating virulence factors and pathogenicity, and for interaction with other commensals influencing the microbiome profiles. Bacteria also produce biogenic amines through aromatic amino acid decarboxylation which is widely expressed in human commensals. These biogenic amines are capable of interacting with adrenergic receptors, leading to a variety of different effects on the human body. Phenylacetyl acid is another compound produced by bacteria found in the gut that acts as a precursor of phenylacetylglutamine, a compound that has been linked to cardiac diseases due to its ability to induce thrombosis by activating adrenergic receptors present in platelets.

A better understanding of the role primary cilia play in the testis is becoming increasingly important in the context of male reproductive health since defects in cilia have been associated with male infertility and reproductive disorders. Primary cilia are found on most somatic cell types within the testis, including Sertoli cells, peritubular myoid cells, and Leydig cells, especially during embryonic and neonatal stages. Primary cilia are involved in signaling pathways that are important for differentiation and function of testicular somatic cells, and cilia are also implicated in testicular morphogenesis. These observations indicate that testicular primary cilia play an integral role in regulating testis development and function.