ABSTRACT
The scientific community widely recognizes that "sex" is a complex category composed of multiple physiologies. Yet in practice, basic scientific research often treats "sex" as a single, internally consistent, and often binary variable. This practice occludes important physiological factors and processes, and thus limits the scientific value of our findings. In human-oriented biomedical research, the use of simplistic (and often binary) models of sex ignores the existence of intersex, trans, non-binary, and gender non-conforming people and contributes to a medical paradigm that neglects their needs and interests. More broadly, our collective reliance on these models legitimizes a false paradigm of human biology that undergirds harmful medical practices and anti-trans political movements. Herein, we continue the conversations begun at the SBN 2022 Symposium on Hormones and Trans Health, providing guiding questions to help scientists deconstruct and rethink the use of "sex" across the stages of the scientific method. We offer these as a step toward a scientific paradigm that more accurately recognizes and represents sexed physiologies as multiple, interacting, variable, and unbounded by gendered preconceptions. We hope this paper will serve as a useful resource for scientists who seek a new paradigm for researching and understanding sexed physiologies that improves our science, widens the applicability of our findings, and deters the misuse of our research against marginalized groups.
Subject(s)
Biomedical Research , Transsexualism , Humans , Neuroendocrinology , Gender Identity , CommunicationABSTRACT
Advances in the knowledge of the neuroendocrine system are closely related to the development of cellular imaging and labeling techniques. This synergy ranges from the staining techniques that allowed the first characterizations of the anterior pituitary gland, its relationship with the hypothalamus, and the birth of neuroendocrinology; through the development of fluorescence microscopy applications, specific labeling strategies, transgenic systems, and intracellular calcium sensors that enabled the study of processes and dynamics at the cellular and tissue level; until the advent of super-resolution microscopy, miniscopes, optogenetics, fiber photometry, and other imaging methods that allowed high spatiotemporal resolution and long-term three-dimensional cellular activity recordings in living systems in a conscious and freely moving condition. In this review, we briefly summarize the main contributions of cellular imaging techniques that have allowed relevant advances in the field of neuroendocrinology and paradigm shifts that have improved our understanding of the function of the hypothalamic-pituitary axes. The development of these methods and equipment is the result of the integration of knowledge achieved by the integration of several disciplines and effort to solve scientific questions and problems of high impact on health and society that this system entails.
Subject(s)
Hypothalamus , Neuroendocrinology , Neurosecretory Systems , Diagnostic ImagingABSTRACT
The incidence of sporadic Alzheimer's disease (AD) is increasing in recent years. Studies have shown that in addition to some genetic abnormalities, the majority of AD patients has a history of long-term exposure to risk factors. Neuroendocrine related risk factors have been proved to be strongly associated with AD. Long-term hormone disorder can have a direct detrimental effect on the brain by producing an AD-like pathology and result in cognitive decline by impairing neuronal metabolism, plasticity and survival. Traditional Chinese Medicine(TCM) may regulate the complex process of endocrine disorders, and improve metabolic abnormalities, as well as the resulting neuroinflammation and oxidative damage through a variety of pathways. TCM has unique therapeutic advantages in treating early intervention of AD-related neuroendocrine disorders and preventing cognitive decline. This paper reviewed the relationship between neuroendocrine and AD as well as the related TCM treatment and its mechanism. The advantages of TCM intervention on endocrine disorders and some pending problems was also discussed, and new insights for TCM treatment of dementia in the future was provided.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Hormones , Humans , Medicine, Chinese Traditional , NeuroendocrinologyABSTRACT
Animal models remain essential to understand the fundamental mechanisms of physiology and pathology. Particularly, the complex and dynamic nature of neuroendocrine cells of the hypothalamus make them difficult to study. The neuroendocrine systems of the hypothalamus are critical for survival and reproduction, and are highly conserved throughout vertebrate evolution. Their roles in controlling body metabolism, growth and body composition, stress, electrolyte balance, and reproduction, have been intensively studied, and have yielded groundbreaking discoveries. Many of these discoveries would not have been feasible without the use of the domestic sheep (Ovis aries). The sheep has been used for decades to study the neuroendocrine systems of the hypothalamus and has become a model for human neuroendocrinology. The aim of this chapter is to review some of the profound biomedical discoveries made possible by the use of sheep. The advantages and limitations of sheep as a neuroendocrine model will be discussed. While no animal model can perfectly recapitulate a human disease or condition, sheep are invaluable for enabling manipulations not possible in human subjects and isolating physiologic variables to garner insight into neuroendocrinology and associated pathologies.
Subject(s)
Hypothalamus , Neuroendocrinology , Animals , Humans , Hypothalamus/metabolism , Neurosecretory Systems/metabolism , Reproduction , SheepABSTRACT
The central brain region of interest for neuroendocrinology is the hypothalamus, a name coined by Wilhelm His in 1893. Neuroendocrinology is the discipline that studies hormone production by neurons, the sensitivity of neurons for hormones, as well as the dynamic, bidirectional interactions between neurons and endocrine glands. These interactions do not only occur through hormones, but are also partly accomplished by the autonomic nervous system that is regulated by the hypothalamus and that innervates the endocrine glands. A special characteristic of the hypothalamus is that it contains neuroendocrine neurons projecting either to the neurohypophysis or to the portal vessels of the anterior lobe of the pituitary in the median eminence, where they release their neuropeptides or other neuroactive compounds into the bloodstream, which subsequently act as neurohormones. In the 1970s it was found that vasopressin and oxytocin not only are released as hormones in the circulation but that their neurons project to other neurons within and outside the hypothalamus and function as neurotransmitters or neuromodulators that regulate central functions, including the autonomic innervation of all our body organs. Recently magnocellular oxytocin neurons were shown to send not only an axon to the neurohypophysis, but also axon collaterals of the same neuroendocrine neuron to a multitude of brain areas. In this way, the hypothalamus acts as a central integrator for endocrine, autonomic, and higher brain functions. The history of neuroendocrinology is described in this chapter from the descriptions in De humani corporis fabrica by Vesalius (1537) to the present, with a timeline of the scientists and their findings.
Subject(s)
Hypothalamus , Neuroendocrinology/history , Oxytocin , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Neurons , Neurosecretory Systems , Pituitary GlandABSTRACT
In most species, survival relies on the hypothalamic control of endocrine axes that regulate critical functions such as reproduction, growth, and metabolism. For decades, the complexity and inaccessibility of the hypothalamic-pituitary axis has prevented researchers from elucidating the relationship between the activity of endocrine hypothalamic neurons and pituitary hormone secretion. Indeed, the study of central control of endocrine function has been largely dominated by 'traditional' techniques that consist of studying in vitro or ex vivo isolated cell types without taking into account the complexity of regulatory mechanisms at the level of the brain, pituitary and periphery. Nowadays, by exploiting modern neuronal transfection and imaging techniques, it is possible to study hypothalamic neuron activity in situ, in real time, and in conscious animals. Deep-brain imaging of calcium activity can be performed through gradient-index lenses that are chronically implanted and offer a 'window into the brain' to image multiple neurons at single-cell resolution. With this review, we aim to highlight deep-brain imaging techniques that enable the study of neuroendocrine neurons in awake animals whilst maintaining the integrity of regulatory loops between the brain, pituitary and peripheral glands. Furthermore, to assist researchers in setting up these techniques, we discuss the equipment required and include a practical step-by-step guide to performing these deep-brain imaging studies.
Subject(s)
Consciousness/physiology , Hypothalamus/diagnostic imaging , Neurosecretory Systems/diagnostic imaging , Animals , Brain , Humans , Hypothalamus/cytology , Neuroendocrinology/methods , Neurosecretory Systems/metabolismABSTRACT
Obesity is associated with the activation of cellular responses, such as endoplasmic reticulum (ER) stress. Here, we show that leptin-deficient ob/ob mice display elevated hypothalamic ER stress as early as postnatal day 10, i.e., prior to the development of obesity in this mouse model. Neonatal treatment of ob/ob mice with the ER stress-relieving drug tauroursodeoxycholic acid (TUDCA) causes long-term amelioration of body weight, food intake, glucose homeostasis, and pro-opiomelanocortin (POMC) projections. Cells exposed to ER stress often activate autophagy. Accordingly, we report that in vitro induction of ER stress and neonatal leptin deficiency in vivo activate hypothalamic autophagy-related genes. Furthermore, genetic deletion of autophagy in pro-opiomelanocortin neurons of ob/ob mice worsens their glucose homeostasis, adiposity, hyperphagia, and POMC neuronal projections, all of which are ameliorated with neonatal TUDCA treatment. Together, our data highlight the importance of early life ER stress-autophagy pathway in influencing hypothalamic circuits and metabolic regulation.
Subject(s)
Autophagy/physiology , Endoplasmic Reticulum Stress/physiology , Energy Metabolism/physiology , Hypothalamus/metabolism , Leptin/metabolism , Neurogenesis/physiology , Adiposity , Animals , Antiviral Agents/pharmacology , Autophagy/drug effects , Autophagy/genetics , Autophagy-Related Protein 7/genetics , Body Weight/drug effects , Body Weight/physiology , Cholagogues and Choleretics/pharmacology , Disease Models, Animal , Eating , Endoplasmic Reticulum Stress/drug effects , Energy Metabolism/drug effects , Energy Metabolism/genetics , Feeding Behavior , Homeostasis , Hyperphagia/metabolism , Leptin/genetics , Male , Metabolic Diseases/genetics , Metabolic Diseases/metabolism , Mice , Mice, Inbred Strains , Mice, Knockout , Neuroendocrinology , Neurogenesis/drug effects , Obesity/metabolism , Pro-Opiomelanocortin/metabolism , Taurochenodeoxycholic AcidABSTRACT
Dirk Hellhammer and his colleagues have played a major role in creating the field of psychoneuroendocrinology from their roots in psychology. In this review, using examples from the history of the McEwen laboratory and neuroscience and neuroendocrinology colleagues, I summarize my own perspective as to how the fields of neuroscience and neuroendocrinology have contributed to psychoneuroendocrinology and how they converged with the contributions from Dirk Hellhammer and his colleagues.
Subject(s)
Allostasis/physiology , Glucocorticoids/physiology , Hypothalamo-Hypophyseal System , Neuroendocrinology , Neuronal Plasticity/physiology , Neurosciences , Psychology, Clinical , Psychoneuroimmunology , Stress, Psychological , History, 20th Century , History, 21st Century , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Neuroendocrinology/history , Neurosciences/history , Psychology, Clinical/history , Psychoneuroimmunology/history , Stress, Psychological/metabolism , Stress, Psychological/physiopathologyABSTRACT
Recent findings have deeply changed the current view of coronary heart disease, going beyond the simplistic model of atherosclerosis as a passive process involving cholesterol build-up in the subintimal space of the arteries until their final occlusion and/or thrombosis and instead focusing on the key roles of inflammation and the immune system in plaque formation and destabilization. Chronic inflammation is a typical hallmark of cardiac disease, worsening outcomes irrespective of serum cholesterol levels. Low-grade chronic inflammation correlates with higher incidence of several non-cardiac diseases, including depression, and chronic depression is now listed among the most important cardiovascular risk factors for poor prognosis among patients with myocardial infarction. In this review, we include recent evidence describing the immune and endocrine properties of the heart and their critical roles in acute ischaemic damage and in post-infarct myocardial remodeling. The importance of the central and autonomic regulation of cardiac functions, namely, the neuro-cardiac axis, is extensively explained, highlighting the roles of acute and chronic stress, circadian rhythms, emotions and the social environment in triggering acute cardiac events and worsening heart function and metabolism in chronic cardiovascular diseases. We have also included specific sections related to stress-induced myocardial ischaemia measurements and stress cardiomyopathy. The complex network of reciprocal interconnections between the heart and the main biological systems we have presented in this paper provides a new vision of cardiovascular science based on psychoneuroendocrineimmunology.
Subject(s)
Coronary Artery Disease/immunology , Heart/physiology , Inflammation , Myocardial Ischemia/immunology , Myocardium/metabolism , Neuroendocrinology , Psychoneuroimmunology , Stress, Psychological , Animals , Circadian Rhythm , Coronary Artery Disease/psychology , Humans , Lipid Metabolism , Myocardial Ischemia/psychology , Risk Factors , Social EnvironmentABSTRACT
The neuroendocrine systems of the hypothalamus are critical for survival and reproduction, and are highly conserved throughout vertebrate evolution. Their roles in controlling body metabolism, growth and body composition, stress, electrolyte balance and reproduction have been intensively studied, and have yielded a rich crop of original and challenging insights into neuronal function, insights that circumscribe a vision of the brain that is quite different from conventional views. Despite the diverse physiological roles of pituitary hormones, most are secreted in a pulsatile pattern, but arising through a variety of mechanisms. An important exception is vasopressin which uses bursting neural activity, but produces a graded secretion response to osmotic pressure, a sustained robust linear response constructed from noisy, nonlinear components. Neuroendocrine systems have many features such as multiple temporal scales and nonlinearity that make their underlying mechanisms hard to understand without mathematical modelling. The models presented here cover the wide range of temporal scales involved in these systems, including models of single cell electrical activity and calcium dynamics, receptor signalling, gene expression, coordinated activity of neuronal networks, whole-organism hormone dynamics and feedback loops, and the menstrual cycle. Many interesting theoretical approaches have been applied to these systems, but important problems remain, at the core the question of what is the true advantage of pulsatility.
Subject(s)
Models, Neurological , Neuroendocrinology , Neurosecretory Systems/physiology , Adrenocorticotropic Hormone/physiology , Animals , Female , Gonadotropins, Pituitary/physiology , Growth Hormone/physiology , Humans , Hypothalamus/physiology , Male , Mathematical Concepts , Milk Ejection/physiology , Neurosecretion/physiology , Oxytocin/physiology , Pituitary Gland/physiology , Pregnancy , Prolactin/physiology , Thyrotropin/physiology , Vasopressins/physiologyABSTRACT
At the beginning of the twentieth century, the hypothalamus was known merely as an anatomical region of the brain lying beneath the thalamus. An increasing number of clinicopathological reports had shown the association of diabetes insipidus and adiposogenital dystrophy (Babinski-Fröhlich's syndrome), with pituitary tumors involving the infundibulum and tuber cinereum, two structures of the basal hypothalamus. The French physicians Jean Camus (1872-1924) and Gustave Roussy (1874-1948) were the first authors to undertake systematic, controlled observations of the effects of localized injuries to the basal hypothalamus in dogs and cats by pricking the infundibulo-tuberal region (ITR) with a heated needle. Their series of surgical procedures, performed between 1913 and 1922, allowed them to claim that both permanent polyuria and adiposogenital dystrophy were symptoms caused by damage to the ITR. Their results challenged the dominant doctrine of hypopituitarism as cause of diabetes insipidus and adiposogenital dystrophy that derived from the experiments performed by Paulescu and Cushing a decade earlier. With their pioneering research, Camus and Roussy influenced the experimental work on the hypothalamus performed by Percival Bailey and Frederic Bremer at Cushing's laboratory, confirming the hypothalamic origin of these symptoms in 1921. More importantly, they provided the foundations for the physiological paradigm of Neuroendocrinology, the hypothalamus' control over the endocrine secretions of the pituitary gland, as well as over water balance and fat metabolism. This article aims to credit Camus and Roussy for their groundbreaking, decisive contributions to postulate the hypothalamus being the brain region in control of endocrine homeostasis and energy metabolism.
Subject(s)
Hypothalamus/metabolism , Pituitary Gland/metabolism , Animals , Cats , Diabetes Insipidus/metabolism , Diabetes Insipidus/pathology , Dogs , Endocrine System/metabolism , Endocrine System/pathology , Humans , Hypothalamic Diseases/metabolism , Hypothalamic Diseases/pathology , Hypothalamus/pathology , Neuroendocrinology , Pituitary Gland/pathology , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathologySubject(s)
Brain/metabolism , Glucose/metabolism , Lipid Metabolism , Neurosecretory Systems/metabolism , Reproduction/physiology , Brain/physiology , Feeding Behavior , Gene Expression Regulation , Gonadotropin-Releasing Hormone , Humans , Hypothalamus/metabolism , Hypothalamus/physiology , Insulin/metabolism , MicroRNAs , Neuroendocrinology , Neuroglia/metabolism , Neuroglia/physiology , Neurosecretory Systems/physiology , Neurotensin/metabolismABSTRACT
Cutting-edge experiments show a new means to control the activity of specifically genetically targeted neurons in the hypothalamus using electromagnetic force. At the flip of a switch, the system bidirectionally regulates feeding behavior and glucose homeostasis, demonstrating wireless control over deep brain regions and their strong influence over energy balance.
Subject(s)
Hypothalamus , Neuroendocrinology , Energy Metabolism , Feeding Behavior , Glucose , HomeostasisABSTRACT
Geoffrey Harris is chiefly known for his demonstration of the control of the pituitary gland by the portal vessels coming from the hypothalamus. This does not do justice to his extraordinary contribution to biology. Harris' life's work was central in demonstrating the brain/body interactions by which animals and humans adapt to their environment, and above all the control of that most crucial and proximate of all evolutionary events - reproduction. In this brief review, I have tried to put Geoffrey Harris' work in the context of the scientific thinking at the time when he began his work, and above all, the contribution of his mentor, FHA Marshall, on whose towering shoulders Harris rose. But this is mainly my personal story, in which I have tried to show the debt that my work owed to Harris and especially to my dear friend, the late Keith Brown-Grant in Harris' team. I myself was never an endocrinologist, but over a short period in the early 1970s, under the influence of such inspirational mentors, and using purely anatomical methods, I was able to demonstrate sexual dimorphism and hormone-dependent sexual differentiation in the connections of the preoptic area, regeneration of the median eminence, the ultrastructure of apoptosis, the requirement for the suprachiasmatic nuclei in reproductive rhythms, the existence of non-rod or cone photoreceptors in the albino rat retina and, later, the expression of vasopressin by solitary (one in 600) magnocellular neurons in the polydipsic di/di Brattleboro mutant rat; this phenomenon was subsequently shown to be due to a+1 reading frameshift. I end this brief overview by mentioning some of the abiding and fascinating mysteries of the endocrine memory of the brain that arise from Harris' work on the control of the endocrines, and by pointing out how the current interest in chronobiology emphasises what a Cinderella the endocrine mechanisms have become in current brain imaging studies.
Subject(s)
Hypothalamus/physiology , Neuroendocrinology/history , Sex Differentiation/physiology , Animals , Female , History, 20th Century , Male , RatsABSTRACT
This review presents the findings that led to the discovery of TRH and the understanding of the central mechanisms which control hypothalamus-pituitary-thyroid axis (HPT) activity. The earliest studies on thyroid physiology are now dated a century ago when basal metabolic rate was associated with thyroid status. It took over 50 years to identify the key elements involved in the HPT axis. Thyroid hormones (TH: T4 and T3) were characterized first, followed by the semi-purification of TSH whose later characterization paralleled that of TRH. Studies on the effects of TH became possible with the availability of synthetic hormones. DNA recombinant techniques facilitated the identification of all the elements involved in the HPT axis, including their mode of regulation. Hypophysiotropic TRH neurons, which control the pituitary-thyroid axis, were identified among other hypothalamic neurons which express TRH. Three different deiodinases were recognized in various tissues, as well as their involvement in cell-specific modulation of T3 concentration. The role of tanycytes in setting TRH levels due to the activity of deiodinase type 2 and the TRH-degrading ectoenzyme was unraveled. TH-feedback effects occur at different levels, including TRH and TSH synthesis and release, deiodinase activity, pituitary TRH-receptor and TRH degradation. The activity of TRH neurons is regulated by nutritional status through neurons of the arcuate nucleus, which sense metabolic signals such as circulating leptin levels. Trh expression and the HPT axis are activated by energy demanding situations, such as cold and exercise, whereas it is inhibited by negative energy balance situations such as fasting, inflammation or chronic stress. New approaches are being used to understand the activity of TRHergic neurons within metabolic circuits.
Subject(s)
Hypothalamo-Hypophyseal System/metabolism , Pituitary Gland/metabolism , Thyroid Gland/metabolism , Thyroid Hormones/metabolism , Thyrotropin-Releasing Hormone/metabolism , Animals , Humans , Hypothalamus/metabolism , NeuroendocrinologyABSTRACT
The birth of clinical neuroendocrinology can be dated to the year 1900, when the French neurologist Joseph Babinski (1857-1932) described a particular syndrome of adiposity and sexual infantilism in an adolescent with a craniopharyngioma expanding at the base of the brain. This condition of adipose-genital dystrophy, also known as Babinski-Fröhlich syndrome, represented the first clinical evidence that the brain controlled endocrine functions. Adipose-genital dystrophy forms part of infundibulo-tuberal syndrome, which groups the endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and the adjacent basal hypothalamus (tuber cinereum). This syndrome was originally described by the French neuropsychiatrists Henri Claude (1869-1946) and Jean Lhermitte (1877-1959) in 1917, also in a patient with a craniopharyngioma. This type of tumor involves specifically the infundibulo-tuberal region of the hypothalamus, providing a clinical model to conceptualize the separation of hypophyseal and hypothalamic functions. The French School of Neurology analyzed and reported the symptoms associated with dysfunction of the basal hypothalamus by craniopharyngiomas and other types of tumors, influencing significantly the development of clinical neuroendocrinology. Experimental lesions performed in the tuber cinereum by the French physiologists Jean Camus (1872-1924) and Gustave Roussy (1874-1948) demonstrated unmistakably the anatomical origin of infundibulo-tuberal syndrome in the basal hypothalamus. This article reviews the original findings on infundibulo-tuberal syndrome reported by the French School of Neurology in the first decades of the twentieth century and the great influence this school had on modern conceptions of hypothalamic control over endocrine functions and behavior.
Subject(s)
Neuroendocrinology/history , Craniopharyngioma/diagnosis , France , History, 19th Century , History, 20th Century , Humans , Hypothalamus/pathology , Pituitary Neoplasms/diagnosisABSTRACT
In November 1955, Geoffrey Harris published a paper based on the Christian A Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore, MD, USA. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing so, Harris introduced a set of properties that helped define the neuroendocrine hypothalamus. They included: i) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; ii) an analogy between the representation of body parts in the sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and the pituitary stalk functions as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons must pass in order to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries that were being made in the early 1950s were beginning to influence neuroendocrinology? This Thematic Review discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and, within this framework, how novel and powerful techniques are currently taking our understanding of the structure of the neuroendocrine hypothalamus to new levels.
Subject(s)
Hypothalamo-Hypophyseal System/anatomy & histology , Hypothalamus/anatomy & histology , Pituitary Gland/anatomy & histology , Animals , Humans , NeuroendocrinologyABSTRACT
This review provides an outline of how our understanding of the neuroendocrine control of the hypothalamo-pituitary-gonadal axis has evolved since the publication of Geoffrey Harris' renowned monograph in 1955. Particular attention is directed to the neurobiology underlying pulsatile GnRH release from the hypothalamus, the neuroendocrine control of ovarian cycles, puberty and seasonality of gonadal function, and to ideas that have emerged as a result of examining the relationship between growth and the reproductive axis. The review closes with i) a brief discussion of how knowledge gained as a result of pursuing the early hypotheses of Harris has led to major clinical and therapeutic applications, and ii) a personal glimpse into the future of research in this fascinating area of biology.
Subject(s)
Gonads/metabolism , Hypothalamo-Hypophyseal System/metabolism , Hypothalamus/metabolism , Pituitary Gland/metabolism , Reproduction/physiology , Sexual Maturation/physiology , Animals , Humans , NeuroendocrinologyABSTRACT
This chapter is based on the Geoffrey Harris Memorial Lecture presented at the 8th International Congress of Neuroendocrinology, which was held in Sydney, August 2014. It provides the development of our understanding of the neuroendocrine control of puberty since Harris proposed in his 1955 monograph (Harris, 1955) that "a major factor responsible for puberty is an increased rate of release of pituitary gonadotrophin" and posited "that a neural (hypothalamic) stimulus, via the hypophysial portal vessels, may be involved." Emphasis is placed on the neurobiological mechanisms governing puberty in highly evolved primates, although an attempt is made to reverse translate a model for the timing of puberty in man and monkey to non-primate species.