Introduction to neuroendocrinology

Neuroendocrinology is the study of the interactions between the nervous system and the endocrine system. The concept arose from the recognition that the secretion of hormones from the pituitary gland was closely controlled by the brain, and especially by the hypothalamus.

Pioneers of neuroendocrinology
Geoffrey Wingfield Harris (1913-1971) is considered by many to be the 'mother' of Neuroendocrinology. Geoffrey Harris is credited as showing that the anterior pituitary gland of mammals is regulated by factors secreted by hypothalamic neurons into the hypothalamo-hypophysial portal circulation. By contrast, the hormones of the posterior pituitary gland are secreted into the systemic circulation directly from the nerve endings of hypothalamic neurons.

The first of these factors to be identified were thyrotropin-releasing hormone (TRH) and gonadotropin releasing hormone (GnRH). TRH is a small peptide that stimulates the secretion of thyroid stimulating hormone (TSH); GnRH (also called luteinising hormone releasing hormone, LHRH) stimulates the secretion of luteinizing hormone and follicle stimulating hormone (FSH).

Roger Guillemin and Andrew W. Schally isolated these factors from the hypothalamus of sheep and pigs, and then identified their structures. Guillemin and Schally were awarded the Nobel Prize in Physiology and Medicine in 1977 for their contributions to understanding "the peptide hormone production of the brain."

Neuroendocrine systems of the hypothalamus
Oxytocin and vasopressin, the two peptide hormones of the posterior pituitary gland (the neurohypophysis), are secreted from the nerve endings of magnocellular neurosecretory neurons into the systemic circulation. The cell bodies of these oxytocin and vasopressin neurons are in the supraoptic nucleus and the paraventricular nucleus, and the electrical activity of these neurons is regulated by afferent synaptic inputs from other brain regions. By contrast, the hormones of the anterior pituitary gland (the adenohypophysis) are secreted from endocrine cells that, in mammals, are not directly innervated, yet the secretion of these hormones (adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin and growth hormone) remains under the control of the brain. The brain controls the anterior pituitary gland by “releasing factors” and “release-inhibiting factors”; these are blood-borne substances released by hypothalamic neurons into blood vessels at the base of the brain, at the median eminence. These vessels, the hypothalamo-hypophysial portal vessels, carry the hypothalamic factors to the adenohypophysis where they bind to specific receptors on the surface of the hormone-producing cells.

For example, the secretion of growth hormone is controlled by two neuroendocrine systems: the growth hormone releasing hormone (GHRH) neurons and the somatostatin neurons, which stimulate and inhibit GH secretion respectively. The GHRH neurones are located in the arcuate nucleus of the hypothalamus, while the somatostatin cells involved in growth hormone regulation are in the periventricular nucleus. These two neuronal systems project axons to the median eminence where they release their peptides into portal blood vessels for transport to the anterior pituitary. Growth hormone is secreted in pulses, which arise from alternating episodes of GHRH release and somatostatin release, which may reflect neuronal interactions between the GHRH and somatostatin cells, and negative feedback from growth hormone.

So why are these systems of interest to physiologists and neuroscientists? Firstly, neuroendocrine systems regulate things that matter to most of us. They control reproduction in all its aspects, from bonding to sexual behavior, they control spermatogenesis and the ovarian cycle, parturition, lactation and maternal behaviour. They control the way we respond to stress and infection. They regulate our metabolism – they influence our eating and drinking behaviour, and influence how the energy intake is utilised – i.e. how fat we get. They influence our mood. They regulate body fluid and electrolyte homeostasis, and blood pressure. In other words, these are systems of central importance to many problems that are major health concerns, as well of sometimes of intimate personal interest.

Secondly, these neurons are large; they are mini “ factories” for producing secretory products; their nerve terminal are large and organised in coherent terminal fields; their output can often be measured easily in the blood; and what these neurons do and what stimuli they respond to are readily open to hypothesis and experiment. For these reasons and more, neuroendocrine neurons are good "model systems" for studying general questions, like “how does a neurone regulate the synthesis, packaging and secretion of its product?” and “how is information encoded in electrical activity?”

The scope of neuroendocrinology
Today, neuroendocrinology embraces a wide range of topics that arose directly or indirectly from the core concept of neuroendocrine neurons. Neuroendocrine neurones control the gonads – and gonadal steroids in turn influence the brain; and so do corticosteroids secreted from the adrenal gland under the influence of ACTH. The study of these feedbacks became naturally the province of neuroendocrinologists. The peptides secreted by hypothalamic neuroendocrine neurons into the blood proved to be released also into the brain, and the central actions often appeared to complement the peripheral actions, so understanding these central actions also became the province of neuroendocrinologists, sometimes even when these peptides cropped up in quite different parts of the brain apparently serving functions unrelated to endocrine regulation. Neuroendocrine neurons were discovered in the peripheral nervous system, regulating for instance digestion. The cells in the adrenal medulla that release adrenaline and noradrenaline proved to have properties between endocrine cells and neurons, and proved to be outstanding model systems for instance for the study of the molecular mechanisms of exocytosis, and these too have become, by extension, “neuroendocrine” systems.

Neuroendocrine systems have been important to our understanding of many basic principles in neuroscience and physiology – for instance our understanding of stimulus-secretion coupling. The origins and significance of patterning in neuroendocrine secretion are still dominant themes in neuroendocrinology today.

Neuroendocrine societies

 * The International Neuroendocrine Federation
 * The American Neuroendocrine Society
 * The British Society for Neuroendocrinology
 * La Societe de Neuroendocrinologie
 * The European Neuroendocrine Association
 * The Japan Neuroendocrine Society

Neuroendocrine journals

 * 'The Journal of Neuroendocrinology' (Blackwell)
 * 'Neuroendocrinology' (Karger)
 * 'Frontiers in Neuroendocrinology' (Academic Press)
 * 'Hormones and Behavior' (Academic Press)
 * 'Neuroendocrinology Letters' (Maghira and Maas Publications)