Current Opinion in Endocrine and Metabolic Research最新文献

Understanding the human hypothalamic-pituitary-gonadal (HPG) axis presents a major challenge for medical science. Dysregulation of the HPG axis is linked to infertility and a thorough understanding of its dynamic behaviour is necessary to both aid diagnosis and to identify the most appropriate hormonal interventions. Here, we review how quantitative models are being used in the context of clinical reproductive endocrinology to: 1. analyse the secretory patterns of reproductive hormones; 2. evaluate the effect of drugs in fertility treatment; 3. aid in the personalization of assisted reproductive technology (ART). In this review, we demonstrate that quantitative models are indispensable tools enabling us to describe the complex dynamic behaviour of the reproductive axis, refine the treatment of fertility disorders, and predict clinical intervention outcomes.

The paraventricular hypothalamic nucleus (PVH) organizes neuroendocrine and autonomic responses to rapidly and slowly developing metabolic stressors that limit their impact on energy balance. The PVH together with the lateral hypothalamic area, and the arcuate and dorsomedial nuclei form a network that is defined by its inputs from medullary catecholamine neurons. These medullary neurons convey important glycemia and glucocorticoid feedback information that is integrated by the PVH and the rest of this network to control a variety of responses to metabolic stressors that have rapid (hypoglycemia) or slow onsets (eating a high calorie diet). This review focuses on how the responses to these two challenges are enabled by these catecholamine neurons, and the integrative nature of the network into which they project.

The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterised by complex dynamics spanning several timescales. This ranges from slow circadian rhythms in blood hormone concentration to faster ultradian pulses of hormone secretion and even more rapid oscillations in electrical and calcium activity in neuroendocrine cells of the hypothalamus and pituitary gland. Here, we focus on the system's oscillations on the short timescale. We highlight some of the mathematical modelling and experimental work that has been carried out to characterise the mechanisms regulating this highly dynamic mode of neuroendocrine signalling and discuss some future directions that may be explored to enhance understanding of HPA function.

Vasomotor symptoms (VMS) result from menopausal hypoestrogenism with subsequent instability of central thermoregulation. VMS cause stress and decreased QOL. Menopausal hormone therapy (MHT) significantly alleviates VMS when compared to placebo or other available non-hormonal options. MHT protects the urogenital system, bone, and cardiovascular system, has beneficial effects on sleep and mood disorders, and may offer protection against colorectal cancer. Negative effects include a risk of thromboembolic disease and the promotion of breast cancer. Adverse effects can be mitigated by initiating MHT within the window of opportunity, using the transdermal route, using estrogen alone or combined with natural progesterone or dydrogesterone, and using the minimum effective dose. Initial findings from the WHI have been widely (and persistently) misinterpreted. Subsequent age-stratified analysis of WHI data indicates that MHT is safe when initiated by women younger than age 60 or within 10 years of menopause onset.

MHT remains the first choice for the treatment of VMS.

Humans and microbes have co-evolved, and the microbial communities we host play an important role in maintaining our health. The human microbiome harbors at least 100 times more genes than the human genome. Thus, these complex communities have a profound effect on our metabolism and physiology thanks to their genetic and metabolic diversity. Our review explores the current understanding of how bacterial metabolism can influence human physiology and pathophysiology. We highlight recent advances in microbiome engineering as well as provide an overview of these engineering technologies and discuss future directions for tool advancements in this promising field. Utilizing these technologies, we can improve our understanding of how microbes affect health and advance personalized therapeutics and nutrition.

The menopausal transition (MT) consists of an early MT (median age at onset 47 years) and late MT (median age at onset 49 years). However, large variation in duration of these stages and their associated symptoms is observed in large samples of women studied over time. There are many proposed biomarkers to predict the onset, progress, and end of the MT. This review will discuss transition staging and the strengths and weaknesses of tests proposed to assist the clinician and patient in predicting the time course of a woman's latter reproductive life span.

Estrogens have been historically considered as the most relevant ovarian hormones for women's general and sexual health. There is, however, growing evidence regarding the important role played by androgens both at central and peripheral levels. Therefore, this review will focus on the role of androgens, particularly testosterone, in sexual health and general well-being in menopausal women.

In the vagina, recent preclinical studies have demonstrated the ability of androgens to positively modulate smooth muscle cell relaxation – fundamental for sexual arousal – and to blunt chronic immuno-inflammatory processes. Furthermore, the female brain is also a crucial sexual organ targeted by androgens.

Future research should address the still controversial role of androgens in affecting female cardiovascular risk and several aspects of women's health.

Recent studies have revealed that adolescence is a period of intense brain plasticity rendering this developmental stage vulnerable to the deleterious effects of stress on mental health. Stress-sensitive brain regions, involved in cognitive and affective processes, are actively developing during this period, through synaptic pruning, myelination, and connectivity between each other. Specific stress reactivity in adolescence may result from the programming effect of previous early life adversities or from exposure to stressors incurred during the peri-adolescent period. In each case, the outcomes are often sex-specific due to difference in genes present on sex chromosomes, sex-specific parent-of-origin gene expression as well as the influence of gonadal hormones that impact brain maturation during development and around puberty. Misreporting of sex dimorphism still exist and need to be solved by better training. More longitudinal clinical analyses are awaited to separate the effect of cumulative stress to the ones occurring specifically at adolescence.