Neuroendocrine function in the hypothalamus

The hypothalamus is the main integrator of endocrine regulation. Glia–neuron interactions contribute to physiological processes such as puberty, the maintenance of bodily homeostasis and ageing. Here, Vincent Prevot and Jerome Clasadonte discuss glia–neuron interactions in the control of hypothalamic neuroendocrine function.

Glucocorticoids are essential for adaptation to stressors (allostasis) and in maladaptation resulting from allostatic load and overload. Here, Bruce McEwen and colleagues discuss the mechanisms of glucocorticoid action in the brain and review how glucocorticoids interact with stress mediators.

An elaborate neural network integrating many internal homeostatic and external signals governs the onset of puberty and subsequent fertility. Here, Allan Herbison provides an update on the morphology and function of the gonadotropin-releasing hormone neurons, focusing on their role in the onset of puberty and fertility.

Activation of AMP-activated protein kinase (AMPK) is dependent on adenosine nucleotides levels in the cell, which vary according to the energy status; AMPK is therefore described as an energy sensor. This Review discusses the role of hypothalamic AMPK in controlling energy balance, and how this knowledge might be used to develop new antiobesity drugs.

In this Review, Lício Velloso and colleagues describe the main components involved in the proteostasis network and consider how defects in these components might interfere with the correct function of the hypothalamus in obesity and ageing.

The hypothalamus and pituitary gland can undergo many functional adaptations to control hormonal output. In this Review, the authors describe our current understanding of the neuroendocrine changes in these structures that maximize reproductive success, and highlight how new imaging techniques have transformed our interpretation of these processes.

In obesity, individuals develop resistance to leptin and ghrelin, which have important functions in the neuroendocrine control of energy homeostasis. Here, Cui and colleagues discuss the mechanisms that lead to leptin and ghrelin resistance, and how they might be exploited as targets for the management and treatment of obesity.

Vincent Prevot and colleagues discuss the role of neuronal nitric oxide (NO) in the regulation of key physiological processes controlled by the preoptic region of the hypothalamus, including reproduction. How deregulation of NO production might be involved in the pathophysiology of brain diseases, for which hormonal imbalances during postnatal development could be a risk factor, is also discussed.

Neuroendocrine networks were previously perceived mainly as transcriptionally controlled, neural regulatory pathways that are centred at the hypothalamus. However, multisystemic circuits encompassing the brain and peripheral tissues have now been uncovered that involve nonneuronal cells and nontranscriptional regulatory mechanisms, with previously unidentified functions, such as reward and behaviour. Several developments in 2016 have helped to consolidate these new advances.

Rapid, minimally invasive control of explicit neural activity would be a major advance for basic and clinical research in the neuroscience and neuroendocrinology fields, and could have applications for the potential treatment of neurological disorders. A new study by Stanley et al. brings us closer to this goal.

In 1998, two children with congenital adrenal insufficiency and early-onset morbid obesity were found to have causative null mutations in POMC. In a new study, therapy with the melanocortin-4 receptor agonist setmelanotide has for the first time brought hope of a normal life to patients with POMC-deficiency.

Although animal models have been used to understand the aetiologies of polycystic ovary syndrome, these models are possibly not the best tool to study the underlying causes of this syndrome, as the disorder is uniquely human and does not occur naturally in animals. A recent study illustrates this point.