An updated field guide for snark hunting: Comparative contributions to behavioral neuroendocrinology in the era of model organisms.

Studying neuroendocrine behavioral regulatory mechanisms in a variety of species across vertebrate groups is critical for determining how they work in natural contexts, how they evolved, and ultimately what can be generalized from them, potentially even to humans. All of the above are difficult, at best, if work within our field is exclusively done in traditional laboratory organisms. The importance of comparative approaches for understanding the relationships between hormones and behavior has been recognized and advocated for since our field's inception through a series of papers centered upon a poetic metaphor of Snarks and Boojums, all of which have articulated the benefits that come from studying a diverse range of species and the risks associated with a narrow focus on "model organisms." This mini-review follows in the footsteps of those powerful arguments, highlighting some of the comparative work since the latest interactions of the metaphor that has shaped how we think about three major conceptual frameworks within our field, two of them formalized - the Organization/Activation Model of sexual differentiation and the Social Brain Network - and one, context-dependency, that is generally associated with virtually all modern understandings of how hormones affect behavior. Comparative approaches are broadly defined as those in which the study of mechanism is placed within natural and/or evolutionary contexts, whether they directly compare different species or not. Studies are discussed in relation to how they have either extended or challenged generalities associated with the frameworks, how they have shaped subsequent work in model organisms to further elucidate neuroendocrine behavioral regulatory mechanisms, and how they have stimulated work to determine if and when similar mechanisms influence behavior in our own species.

The behavioral neuroendocrinology of maternal behavior: Past accomplishments and future directions.

Research on the neuroendocrine-endocrine-neural regulation of maternal behavior has made significant progress the past 50 years. In this mini-review progress during this period has been divided into five stages. These stages consist of advances in the identification of endocrine factors that mediate maternal care, the characterization of the neural basis of maternal behavior with reference to endocrine actions, the impact of developmental and experiential states on maternal care, the dynamic neuroplastic maternal brain, and genes and motherhood. A final section concludes with a discussion of future directions in the field of the neurobiology/neuroendocrinology of motherhood.

Hormones and Behavior: An emergent journal.

Hormones and Behavior was founded in 1969 by Frank A. Beach and members of his laboratory. Prior to the founding there was no journal specifically devoted to hormones and behavior. This paper explores how the editorship of the journal has developed over the first 50 years, going from the initial three male editors to the current female editor-in-chief, five associate editors (four men and one women), and a 98 member editorial board consisting of 46 men and 52 women. Early concerns that a specialty journal of hormones and behavior might ghettoize the field did not come to pass and the visibility and impact of the journal has helped to expand the spread of the field, now called Behavioral Neuroendocrinology. This growth accelerated with the creation of the Society for Behavioral Neuroendocrinology in 1996 and the adoption of Hormones and Behavior as the Society's official journal. The growth has been striking with total annual citations going from 1321 per year in 1997 to the current 10,874 annual citations. The journal's impact factor (JIF), 1.42 in 1997, has increased to the current (2018) JIF of 3.95. Over the 50 years of Hormones and Behavior's existence it has emerged as a principle voice of the Hormones and Behavior community. It will be intriguing to see what the next 50 years reveals.

Dads: Progress in understanding the neuroendocrine basis of human fathering behavior.

We outline the progress on the hormonal basis of human paternal behavior during the past twenty years. Advances in understanding the roles of testosterone, prolactin, oxytocin and vasopressin in fathering behavior are described, along with recent research on hormonal interactions, such as those between testosterone and cortisol, and testosterone and the peptide hormones. In addition, we briefly describe the recent leaps forward in elucidating the neurobiological and neuroendocrine basis of fatherhood, made possible by fMRI technology. Emerging from this literature is a developing and complicated story about fatherhood, highlighting the need to further understand the interplay between behavior, physiology, social context, and individual genetic variation. Given the changing roles of parents in many societies, the continued growth of this research area will provide a strong empirical knowledge base about paternal behavior on which to create policies promoting fathers' involvement in their infants' lives.

Sexual differentiation of brain and other tissues: Five questions for the next 50 years.

This paper is part of the celebration of the 50th anniversary of founding of the journal Hormones and Behavior, the official journal of the Society for Behavioral Neuroendocrinology. All sex differences in phenotypic development stem from the sexual imbalance in X and Y chromosomes, which are the only known differences in XX and XY zygotes. The sex chromosome genes act within cells to cause differences in phenotypes of XX and XY cells throughout the body. In the gonad, they determine the type of gonad, leading to differences in secretion of testicular vs. ovarian hormones, which cause further sex differences in tissue function. These current ideas of sexual differentiation are briefly contrasted with a hormones-only view of sexual differentiation of the last century. The multiple, independent action of diverse sex-biasing agents means that sex-biased factors can be synergistic, increasing sex differences, or compensatory, making the two sexes more equal. Several animal models have been fruitful in demonstrating sex chromosome effects, and interactions with gonadal hormones. MRI studies of human brains demonstrate variation in brain structure associated with both differences in gonadal hormones, and in the number of X and Y chromosomes. Five unanswered questions are posed as a challenge to future investigators to improve understanding of sexual differentiation throughout the body.

Testosterone administration in human social neuroendocrinology: Past, present, and future.

Over the past 20 years, social neuroendocrinology researchers have developed pharmacological challenge paradigms to assess the extent to which testosterone plays a causal role in human psychological and behavioural processes. The current paper provides a brief summary of this research and offers recommendations for future research examining the neuroendocrine mechanisms underlying human behaviour.

How technical progress reshaped behavioral neuroendocrinology during the last 50 years and some methodological remarks.

The first issue of Hormones and Behavior was published 50 years ago in 1969, a time when most of the techniques we currently use in Behavioral Endocrinology were not available. Researchers have during the last 5 decades developed techniques that allow measuring hormones in small volumes of biological samples, identify the sites where steroids act in the brain to activate sexual behavior, characterize and quantify gene expression correlated with behavior expression, modify this expression in a specific manner, and manipulate the activity of selected neuronal populations by chemogenetic and optogenetic techniques. This technical progress has considerably transformed the field and has been very beneficial for our understanding of the endocrine controls of behavior in general, but it did also come with some caveats. The facilitation of scientific investigations came with some relaxation of methodological exigency. Some critical controls are no longer performed on a regular basis and complex techniques supplied as ready to use kits are implemented without precise knowledge of their limitations. We present here a selective review of the most important of these new techniques, their potential problems and how they changed our view of the hormonal control of behavior. Fortunately, the scientific endeavor is a self-correcting process. The problems have been identified and corrections have been proposed. The next decades will obviously be filled with exciting discoveries in behavioral neuroendocrinology.

Mini-review: Epigenetic mechanisms that promote transgenerational actions of endocrine disrupting chemicals: Applications to behavioral neuroendocrinology.

It is our hope this mini-review will stimulate discussion and new research. Here we briefly examine the literature on transgenerational actions of endocrine disrupting chemicals (EDCs) on brain and behavior and their underlying epigenetic mechanisms including: DNA methylation, histone modifications, and non-coding RNAs. We stress that epigenetic modifications need to be examined in a synergistic manner, as they act together in situ on chromatin to change transcription. Next we highlight recent work from one of our laboratories (VGC). The data provide new evidence that the sperm genome is poised for transcription. In developing sperm, gene enhancers and promoters are accessible for transcription and these activating motifs are also found in preimplantation embryos. Thus, DNA modifications associated with transcription factors during fertilization, in primordial germ cells (PGCs), and/or during germ cell maturation may be passed to offspring. We discuss the implications of this model to EDC exposures and speculate on whether natural variation in hormone levels during fertilization and PGC migration may impart transgenerational effects on brain and behavior. Lastly we discuss how this mechanism could apply to neural sexual differentiation.

Estrogenic regulation of memory: The first 50 years.

This review highlights fifty years of progress in research on estradiol's role in regulating behavior(s). It was initially thought that estradiol was only involved in regulating estrus/menstrual cycles and concomitant sexual behavior, but it is now clear that estradiol also influences the higher order neural function of cognition. We provide a brief overview of estradiol's regulation of memory and some mechanisms which underlie its effects. Given systemically or directly into the hippocampus, to ovariectomized female rodents, estradiol or specific agonists, enhance learning and/or memory in a variety of rodent cognitive tasks. Acute (within minutes) or chronic (days) treatments enhance cognitive functions. Under the same treatment conditions, dendritic spine density on pyramidal neurons in the CA1 area of the hippocampus and medial prefrontal cortex increase which suggests that these changes are an important component of estrogen's ability to impact memory processes. Noradrenergic, dopaminergic and serotoninergic activity are also altered in these areas following estrogen treatments. Memory enhancements and increased spine density by estrogens are not limited to females but are also present in castrate males. In the next fifty years, neuroscientists need to determine how currently described neural changes mediate improved memory, how interactions among areas important for memory promote memory and the potential significance of neurally derived estrogens in normal cognitive processing. Answering these questions may provide significant advances for treatment of dementias as well as age and neuro-degenerative disease related memory loss.

Human social neuroendocrinology: Review of the rapid effects of testosterone.

Contribution to Special Issue on Fast effects of steroids. It is well documented that testosterone concentrations change rapidly within reproductively relevant contexts (e.g., competition, mate-seeking). It has been argued that such rapid changes in testosterone may serve to adaptively fine-tune ongoing and/or future social behaviour according to one's social environment. In this paper, we review human correlational and experimental evidence suggesting that testosterone fluctuates rapidly in response to competition and mate-seeking cues, and that such acute changes may serve to modulate ongoing and/or future social behaviours (e.g., risk-taking, competitiveness, mate-seeking, and aggression). Some methodological details, which limit interpretation of some of this human work, are also discussed. We conclude with a new integrative model of testosterone secretion and behaviour, the Fitness Model of Testosterone Dynamics. Although we focus primarily on human aggression in this review, we also highlight research on risk-taking, competitiveness, and mate-seeking behaviour.

EDTORIAL_.

Why did we prepare this supplement and why it is about interdisciplinary public health issues? It is rather difficult question, but with a simple answer. Neurology field, neuroendocrinology field and many other areas of medicine are actually very important partners for public health professionals. Public health promotes and protects the health of people and the communities where they live, learn, work and play. While doctors treat people who are sick, those of us working in public health try to prevent people from getting sick or injured in the first place.

OLD AND NEW NEUROENDOCRINE MOLECULES: SOMATOSTATIN, CYSTEAMINE, PANTETHINE AND KYNURENINE.

The aim of this review is to commemorate Hans Selye, endocrinologist, the most famous researchers of stress and to briefly summarize the major features of somatostatin (SST), cysteamine (CysA) and patethine (PAN) in neuroendocrinological aspect, which are closely related to his scientific work. In addition, some metabolites of kynurenine pathway (KP) were also mentioned in this paper, as new, possible target molecules in neuroendocrinology. R. Guillemin and A. V. Schally were the main pioneers of the discovery of SST in the 1970's. SST primarily is known as an inhibitor of growth hormone secretion and additionally reduces the gastric acid and pepsin release and also the gastroduodenal mucosal blood flow. These effects are very important in the pathophysiology of peptic ulcer bleeding, which is related to the CysA-evoked perforating duodenal ulcer experimental stress model in rats developed by Selye and Szabo. CysA is a naturally occurring duodenal ulcerogen, which depletes SST in the gastric mucosa and certain brain regions. Furthermore, in addition to depleting SST, CysA also causes adrenocortical necrosis, suggesting an interaction between the central/peripheral nervous system and the neuroendocrine system. The antioxidant PAN, formulated besides the CysA, has similar effects: it attenuates the levels of SST and prolactin in the cerebral cortex and hypothalamus through the accumulation of CysA within cells throughout the body. As new perspectives the KP may be involved in the modulation of neuroendrocrine processes: different agonists and antagonists of glutamate receptors regulate the hypothalamic-pituitary-adrenal axis and kynurenic acid augments the anxiolytic stress responses in neonatal chicks. The pro-inflammatory cytokine-induced and the toxic heavy oil contaminations-evoked alterations in the KP indirectly contribute to the development of neuroendocrine disorders. In summary, there have been highly important developments in neuroendocrinology since the early findings of Selye. Although there are as yet relatively few data about the potential role of kynurenines in neuroendocrinology, the results already achieved are extremely noteworthy and immensely promising.

Neuroendocrinological aspects of epilepsy: important issues and trends in future research.

Neuroendocrine research in epilepsy focuses on the interface among neurology, endocrinology, gynecology/andrology and psychiatry as it pertains to epilepsy. There are clinically important reciprocal interactions between hormones and the brain such that neuroactive hormones can modulate neuronal excitability and seizure occurrence while epileptiform discharges can disrupt hormonal secretion and promote the development of reproductive disorders. An understanding of these interactions and their mechanisms is important to the comprehensive management of individuals with epilepsy. The interactions are relevant not only to the management of seizure disorder but also epilepsy comorbidities such as reproductive dysfunction, hyposexuality and emotional disorders. This review focuses on some of the established biological underpinnings of the relationship and their clinical relevance. It identifies gaps in our knowledge and areas of promising research. The research has led to ongoing clinical trials to develop hormonal therapies for the treatment of epilepsy. The review also focuses on complications of epilepsy treatment with antiepileptic drugs. Although antiepileptic drugs have been the mainstay of epilepsy treatment, they can also have some adverse effects on sexual and reproductive function as well as bone density. As longevity increases, the prevention, diagnosis and treatment of osteoporosis becomes an increasingly more important topic, especially for individuals with epilepsy. The differential effects of antiepileptic drugs on bone density and their various mechanisms of action are reviewed and some guidelines and future directions for prevention of osteoporosis and treatment are presented.

[Neuroendocrine immunology: new pathogenetic aspects and clinical application]. / Neuroendokrinimmunologie: Neue Aspekte zur Pathogenese und Klinischen Anwendung.

After two decades of enormous improvements in anti-inflammatory therapy with biologics long-standing disease sequelae in chronic inflammatory diseases (CID) can be recognized, such as fatigue, anorexia/malnutrition, cachectic obesity, insulin resistance, dyslipidemia, changes of steroid hormone axes (e. g. loss of androgens), increased sympathetic nervous tone/decreased parasympathetic nervous tone, inflammation-related anemia and osteopenia. This article demonstrates for the first time in the German language a new theory to explain the pathophysiology of these disease sequelae. It includes concepts from evolutionary medicine and neuroendocrine regulation of energy allocation. The core statement is: the networks of energy regulation and energy allocation have been evolutionarily positively selected for transient inflammatory episodes (not for CIDs due to the negative selection pressure) but long-standing use of these adaptive programs for CID support systemic disease sequelae. These considerations might help to deviate focus from pure anti-inflammatory treatment to adequate diagnosis and therapy of systemic disease sequelae.

Neuroendocrinology and its quantitative development: a bioengineering view.

Biomedical engineering is clearly present in modern neuroendocrinology, and indeed has come to embrace it in many respects. First, we briefly review the origins of endocrinology until neuroendocrinology, after a long saga, was established in the 1950's decade with quantified results made possible by the radioimmunoassay technique (RIA), a development contributed by the physical sciences. However, instrumentation was only one face of the quantification process, for mathematical models aiding in the study of negative feedback loops, first rather shyly and now at a growing rate, became means building the edifice of mathematical neuroendocrinology while computer assisted techniques help unravel the associated genetic aspects or the nature itself of endocrine bursts by numerical deconvolution analysis. To end the note, attention is called to the pleiotropic characteristics of neuroendocrinology, which keeps branching off almost endlessly as bioengineering does too.