Current Opinion in Endocrine and Metabolic Research最新文献

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.

PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at GABA_A receptors. These neurosteroids modulate neuronal firing rate, regional brain connectivity, and activation of amygdala-mediated autonomic nervous system, hypothalamic–pituitary–adrenal axis, and behavioral reactions to unconditioned and conditioned threat. They also play critical roles in learning and memory processes such as extinction and extinction retention and inhibit toll-like receptor activation of intracellular pro-inflammatory pathways. Deficient synthesis of these neurosteroids thus may contribute to individually variable PTSD clinical phenotypes encompassing symptom severity, capacity for PTSD recovery, and vulnerability to common PTSD-comorbidities such as major depression, chronic pain, alcohol and nicotine dependence, cardiovascular disease, metabolic syndrome, reproductive disorders, and autoimmune conditions.

The anterior pituitary is exposed to ultradian, circadian and stress-induced rhythms of circulating glucocorticoid hormones. Glucocorticoids feedback at the level of the pituitary corticotroph to control their own production through multiple mechanisms. This review highlights key insights from analysis of the dynamics of rapid and early glucocorticoid feedback that reveal both non-genomic and genomic mechanisms mediated by glucocorticoid receptors. Importantly, a common target is control of electrical excitability and calcium signalling although non-genomic effects may also involve control of hormone secretion distal to calcium signalling. Understanding the mechanisms and functional consequences of pulsatile glucocorticoid signalling in the anterior pituitary promises to elucidate the role of glucocorticoids in health and disease, as well as identifying potential diagnostic and therapeutic targets.

Systemic metabolism is regulated by inter-organ communication at the whole-body level, and at the intra-organ level, there are also numerous factors involved in metabolic regulation. Transomic analysis is used to construct a metabolic regulatory network by integrating multiple factors obtained by multiomic analysis with interaction information. This review provides an overview of multiomic technologies and databases for intra- and inter-organ interactions, and discusses methods for constructing inter-organ transomic networks and their applications.