Frontiers in Neuroendocrinology最新文献

Hormonal contraceptives are among the most important health and economic developments in the 20th Century, providing unprecedented reproductive control and a range of health benefits including decreased premenstrual symptoms and protections against various cancers. Hormonal contraceptives modulate neural function and stress responsivity. These changes are usually innocuous or even beneficial, including their effects on mood. However, in approximately 4–10% of users, or up to 30 million people at any given time, hormonal contraceptives trigger depression or anxiety symptoms. How hormonal contraceptives contribute to these responses and who is at risk for adverse outcomes remain unknown. In this paper, we discuss studies of hormonal contraceptive use in humans and describe the ways in which laboratory animal models of contraceptive hormone exposure will be an essential tool for expanding findings to understand the precise mechanisms by which hormonal contraceptives influence the brain, stress responses, and depression risk.

Exposure therapy is a central component of the first-line treatment for anxiety disorders, a common mental health condition that is twice as prevalent in women relative to men. A key underlying mechanism of exposure therapy is fear extinction, which is an active learning process supported by a neural circuitry that is highly regulated by ovarian hormones. This review synthesises research examining the impact of hormonal contraceptives on laboratory fear extinction tasks in female rats and women, and on exposure therapy in women with anxiety disorders. The evidence indicates that hormonal contraceptives have a detrimental impact on fear extinction and exposure therapy that is consistent across species, and from laboratory to clinical settings. Candidate pathways by which hormonal contraceptives impede fear extinction and exposure therapy include suppression of endogenous ovarian hormones and glucocorticoids, and downregulation of signalling pathways that support extinction learning. Key areas of focus for future research are discussed.

Worldwide over 150 million women use oral contraceptives (OCs), which are the most prescribed form of contraception in both the United States and in European countries. Sex hormones, such as estradiol and progesterone, are important endogenous hormones known for shaping the brain across the life span. Synthetic hormones, which are present in OCs, interfere with the natural hormonal balance by reducing the endogenous hormone levels. Little is known how this affects the brain, especially during the most vulnerable times of brain maturation. Here, we review studies that investigate differences in brain gray and white matter in women using OCs in comparison to naturally cycling women. We focus on two neuroimaging methods used to quantify structural gray and white matter changes, namely structural MRI and diffusion MRI. Finally, we discuss the potential of these imaging techniques to advance knowledge about the effects of OCs on the brain and wellbeing in women.

The vertebrate pituitary is a dynamic organ, capable of adapting its hormone secretion to different physiological demands. In this context, endocrinologists have debated for the past 40 years if endocrine cells are mono- or multi-hormonal. Since its establishment, the dominant “one cell, one hormone” model has been continuously challenged. In mammals, the use of advanced multi-staining approaches, sensitive gene expression techniques, and the analysis of tumor tissues have helped to quickly demonstrate the existence of pituitary multi-hormone cells. In fishes however, only recent advances in imaging and transcriptomics have enabled the identification of such cells. In this review, we first describe the history of the discovery of cells producing multiple hormones in mammals and fishes. We discuss the technical limitations that have led to uncertainties and debates. Then, we present the current knowledge and hypotheses regarding their origin and biological role, which provides a comprehensive review of pituitary plasticity.

Research on hormonal contraceptives (HC) in animal models is lacking, and as a result, so is our understanding of the impact of HC on the brain and behavior. Here, we provide a review of the pharmacology of HC, as well as the methodology and best practices for designing a model of HC in female rats. We outline specific methodological considerations regarding dosing, route of administration, exposure time/timing, and selecting a control group. We also provide a framework outlining important levels of analysis for thinking about the impact of HC on behavioral and neurobiological outcomes. The purpose of this review is to equip researchers with foundational knowledge, and some basic elements of experimental design for future studies investigating the impact of HC on the brain and behavior of female rats.

Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic potentiation (LTP)-related pathways, by products induced by physical exercise (i.e., exerkines), is a crucial aspect of the exercise-effect on the brain. This review summarizes synaptic pathways that are activated by exerkines and may potentiate LTP. For a total of 16 exerkines, we indicated how blood and brain exerkine levels are altered depending on the type of physical exercise (i.e., cardiovascular or resistance exercise) and how they respond to a single bout (i.e., acute exercise) or multiple bouts of physical exercise (i.e., chronic exercise). This information may be used for designing individualized physical exercise programs. Finally, this review may serve to direct future research towards fundamental gaps in our current knowledge regarding the biophysical interactions between muscle activity and the brain at both cellular and system levels.

Hormonal contraceptives (HCs), prescribed to millions of women around the world, alter the ovarian hormonal cycle resulting in neurobehavioral changes in HC users. Human epidemiological and experimental data has characterized some of these effects with oftentimes conflicting or irreproducible results, reflecting a dearth of research considering different compositions, routes of administration, or time-courses of HC use. Non-human animal research can model these effects and help elucidate the underlying mechanisms by which different HCs modulate neurobehavioral outcomes. Still, animal models using HCs are not well-established. This may be because the pharmacological profile of HCs – including the metabolism, receptor binding affinity, and neuromodulatory effects – is dynamic and not always clearly translatable between animals and humans. The current review addresses these issues and provides basic methods and considerations for the use of HCs in animal models of neurobehavior to help advance the field of behavioral neuroendocrinology and inform decisions regarding to women’s health.

Around 80% of women worldwide suffer mild Premenstrual Disorders (PMD) during their reproductive life. Up to a quarter are affected by moderate to severe symptoms, and between 3% and 8% experience a severe form. It is classified as premenstrual syndrome (PMS) with predominantly physical symptoms and premenstrual dysphoric disorder (PMDD) with psychiatric symptoms. The present review analyzes the factors associated with PMD and the Hypothalamus-Pituitary-Ovarian or Hypothalamus-Pituitary-adrenal axis and discusses the main animal models used to study PMDD. Evidence shows that the ovarian hormones participate in PMDD symptoms, and several points of regulation of their synthesis, metabolism, and target sites could be altered. PMDD is complex and implies several factors that require consideration when this condition is modeled in animals. Of particular interest are those points related to areas that may represent opportunities to develop new approximations to understand the mechanisms involved in PMDD and possible treatments.

The obligatory role of kisspeptin (KISS1) and its receptor (KISS1R) in regulating the hypothalamic-pituitary–gonadal axis, puberty and fertility was uncovered in 2003. In the few years that followed, an impressive body of work undertaken in many species established that neurons producing kisspeptin orchestrate gonadotropin-releasing hormone (GnRH) neuron activity and subsequent GnRH and gonadotropin hormone secretory patterns, through kisspeptin-KISS1R signaling, and mediate many aspects of gonadal steroid hormone feedback regulation of GnRH neurons. Here, we review knowledge accrued over the past decade, mainly in genetically modified mouse models, of the electrophysiological properties of kisspeptin neurons and their regulation by hormonal feedback. We also discuss recent progress in our understanding of the role of these cells within neuronal circuits that control GnRH neuron activity and GnRH secretion, energy balance and, potentially, other homeostatic and reproductive functions.