Current Opinion in Endocrine and Metabolic Research最新文献

The transition to menopause is a hallmark in women's life, associated with bothersome symptoms like hot flashes, night sweats, sleep problems, and mood disturbances, which compromise the quality of life. Menopause is also associated with chronic diseases like cardiovascular disease and osteoporosis. Managing menopause requires theoretical education on the physiologic underpinnings of menopause, which should be combined with clinical experience in treatment strategies. The current review aimed to illustrate gaps in menopause education in Medical School and specialty training programs, and explore physicians' understanding of the topic. Although menopause education is a topic incorporated in Medical School and specialty training curricula and, although Menopause Societies worldwide provide educational modules, physicians' knowledge and competence remain inadequate. General Medicine specialty training programs should reinforce menopause education as part of their mandatory curricula to improve the skills of trainees in managing women's health issues at every age.

Release of corticotropin-releasing hormone (CRH) from CRH neurons activates the hypothalamo–pituitary–adrenal (HPA) axis, one of the main physiological stress response systems. Complex feedback loops operate in the HPA axis and understanding the neurobiological mechanisms regulating CRH neurons is of great importance in the context of stress disorders. In this article, we review how in vivo studies in zebrafish have advanced knowledge of the neurobiology of CRH neurons. Disrupted-in-schizophrenia 1 (DISC1) mutant zebrafish have blunted stress responses and can be used to model human stress disorders. We propose that DISC1 influences the development and functioning of CRH neurons as a mechanism linking DISC1 to psychiatric disorders.

In response to stress, corticotropin-releasing factor (CRF) neurons located in the paraventricular nucleus of the hypothalamus (PVN) activate the hypothalamic–pituitary–adrenal (HPA) axis. Recently, PVN CRF neurons have been shown to also modulate stress-responsive behavior dynamically, via direct synaptic projections. In addition, a population of CRF receptor 1 (CRFR1) positive neurons were identified in the PVN that respond to local CRF release and project to local, rostral and caudal brain nuclei to influence stress responses. Both direct projections by CRF neurons and local activation of CRFR1+ neurons in the PVN allow CRF neurons that traditionally have been thought to be dedicated to controlling HPA axis activity to also modulate behavior, endocrine and autonomic features of the stress response acutely as a threat unfolds.

To summarize recent evidence of the sociocultural, environmental, behavioral, and biological factors that contribute to disparities and inequities in menopause health.

Racism, discrimination, chronic stress, and trauma are related to more severe menopause symptoms and cardiovascular disease (CVD) risk during the menopause transition (MT). Living in neighborhoods with higher concentrations of air pollution and less greenspace may be associated with a younger age at menopause. These sociocultural and built environments may lead to adverse physiologic changes and health outcomes during the MT, which disproportionately affect women of color.

Emerging literature supports the need to address upstream factors that drive inequities in menopause health including, racism, discrimination, and health care access. Women of color and those who identify as a sexual or gender minority likely perceive and experience the MT differently, but additional research is needed to evaluate this fully.

Stress affects many brain regions, including the ventral tegmental area (VTA), which is critically involved in reward processing. Excessive stress can reduce reward-seeking behaviors but also exacerbate substance use disorders, two seemingly contradictory outcomes. Recent research has revealed that the VTA is a heterogenous structure with diverse populations of efferents and afferents serving different functions. Stress has correspondingly diverse effects on VTA neuron activity, tending to decrease lateral VTA dopamine (DA) neuron activity, while increasing medial VTA DA and GABA neuron activity. Here we review the differential effects of stress on the activity of these distinct VTA neuron populations and how they contribute to decreases in reward-seeking behavior or increases in drug self-administration.

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.