Current Opinion in Endocrine and Metabolic Research最新文献

Hormones regulate metabolic homeostasis through interlinked dynamic networks of proteins and small molecular weight metabolites, and state-of-the-art chemical technologies have been developed to decipher these complex pathways. Stable-isotope tracers have largely replaced radiotracers to measure flux in humans, building on advances in nuclear magnetic resonance spectroscopy and mass spectrometry. These technologies are now being applied to localise molecules within tissues. Radiotracers are still highly valuable both preclinically and in 3D imaging by positron emission tomography. The coming of age of vibrational spectroscopy in conjunction with stable-isotope tracing offers detailed cellular insights to map complex biological processes. Together with computational modelling, these approaches are poised to coalesce into multi-modal platforms to provide hitherto inaccessible dynamic and spatial insights into endocrine signalling.

Genitourinary syndrome of menopause (GSM) is a heterogeneous chronic condition potentially affecting the quality of life (QoL) and sexual health in women at midlife and beyond. A disconnection between signs and symptoms of GSM is evident in clinical studies and everyday practice, as several psychosocial factors may modulate the clinical manifestation of urogenital atrophic changes. A symptom-oriented approach forms the basis of a tailored management, but the prevention of the progressive signs of urogenital ageing seems important in a long-term perspective promoting longevity. In this short review, main data about the effectiveness of evidence-based available treatments on different components of GSM, including vaginal, vulvar and urinary symptoms, as well as on signs of urogenital atrophy, are summarised, highlighting gaps in the literature, which should be addressed to improve evidence-based treatment individualisation.

Stress responses have a major impact on whole body physiology, including energy metabolism, but the underlying neural substrates and pathways mediating stress effects on energy metabolism are complex. The corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus play a central role in stress response. Recently, accumulating evidence indicates that the PVN CRH neurons are a direct link between stress and obesity. Obesity impairs CRH neurons responsiveness to stress, and perturbations of CRH neurons activity cause obesity. Therefore, CRH neurons in the hypothalamus stand at the intersection of stress response and energy balance regulation. Here, we reviewed recent advances in understanding the regulation of appetite and energy metabolism by PVN CRH neurons, with a focus on the distinct long-term contributions of CRH neuropeptides and glucocorticoids.

Much of the centrally available oxytocin (OT) is synthesized in magnocellular neurons located in the paraventricular nucleus of the hypothalamus. This same area is home to parvocellular corticotropin-releasing hormone (CRH) synthesizing neurons that regulate activation of the hypothalamic-pituitary-adrenal (HPA) axis. A large body of data indicates that complex interactions between these systems inextricably link central OT signaling with the neuroendocrine response to stress. This review focuses on a small but diverse set of cellular and synaptic mechanisms that have been proposed to underlie intrahypothalamic OT/CRH interactions during the response to acute stress.

Glucocorticoids exert pleiotropic effects either by a relatively slow mechanism involving binding to cytosolic/nuclear receptors and regulation of gene expression or by rapid activation of a putative membrane receptor and membrane signal transduction. Rapid glucocorticoid actions are initiated at the membrane and recruit intracellular signaling pathways that engage multiple downstream cellular targets, including lipid and gas intercellular messengers, membrane neurotransmitter receptor trafficking, nuclear glucocorticoid receptor activation and trafficking, and more. Thus, membrane glucocorticoid signaling diverges into a multiplexed array of signaling pathways to simultaneously regulate highly diverse cellular functions, giving these steroid hormones a broad range of rapid regulatory capabilities. In this review, we provide a brief overview of the growing body of knowledge of the cell signaling mechanisms of rapid glucocorticoid actions in the brain.

The aim of ovarian stimulation in fertility treatment is to increase the number of large follicles and hence the number of eggs that can be retrieved for in vitro fertilisation (IVF). However, large inter- and intra-individual variability in the menstrual cycle and ovarian response to stimulation drugs complicate treatment planning and prediction. Hence, many mathematical models have been developed to support treatment decisions. In this article, we give an overview of mechanistic models that cover different aspects of the processes involved in normal menstrual cycles and ovarian stimulation, including hormonal regulation and follicular maturation. We also review statistical models that have been designed to predict different IVF outcome criteria. Finally, we outline the use of mathematical models for in-silico clinical trials in reproductive endocrinology.

Ultradian glucocorticoid rhythms are highly conserved across mammalian species and robustly oscillate within a cyclical dynamic signalling network. Despite this, the role of ultradian signalling and the effects of its dysregulation for cognitive processing and metabolic homeostasis is often overlooked within chrono-biological research. This review will discuss ultradian specific signalling and transcriptional mechanisms and the proposed models and repercussion of ultradian dysregulation for cognitive and metabolic function. Highlighting emerging therapeutic treatment that may have significant impacts for future patient care and treatment.

The accurate regulation of glucose within humans is an essential feature of homeostasis. It optimises energy release in the muscles and organs. Glucose rhythms driven by internal and external stimuli have been physiologically observed in humans and modelled mathematically to provide a solid framework for understanding these processes in a qualitative and quantitative manner. In this article, we review the latest contribution of mathematical modelling to the understanding and prediction of dynamics within the glucose regulation system.

Obesity is a chronic disease requiring chronic management. Anti-obesity medication for the treatment of obesity includes the glucagon-like peptide-1 (GLP-1) agonists liraglutide and semaglutide. This review will discuss the results of weight loss clinical trials for these agents, in addition to anorectic gut hormone analogue combinations and co-agonist drugs targeting gut hormone receptors, as well as the implications for the clinical management of obesity.