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Introduction to neuroendocrinology

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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 is closely controlled by the brain, especially by the hypothalamus. It is a field that builds on the knowledge of endocrinology and lays the foundation for psychoneuroendocrinology.

Pioneers of neuroendocrinologyEdit

Berta Scharrer (1906-1995) Co-Founder of Neuroendocrinocology.

Geoffrey Harris [1] (1913-1971) is considered by many to be the "father" of neuroendocrinology. Geoffrey Harris is credited with showing that the anterior pituitary gland of mammals is regulated by factors secreted by hypothalamic neurons into the hypothalamohypophysial 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 are 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."

In 1952, Andor Szentivanyi and Geza Filipp wrote the world's first research paper showing how neural control of immunity takes place through the hypothalamus. http://home.cc.umanitoba.ca/~berczii/dr_szentivanyi_memorial/szentivanyi_memorial.htm

Neuroendocrine systems of the hypothalamusEdit

Oxytocin and vasopressin/anti-diuretic hormone, 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 paraventricular nucleus and supraoptic nucleus, respectively, 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, whereas 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.

Gonadotropin-releasing hormone (GnRH) also secreted from nerve terminals in the median eminence serves to stimulate the release of the pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn promote gonadal steroid production. The cell bodies for GnRH neurons are located in more rostral hypothalamic areas, and various factors are now known to regulate its synthesis and secretion. One type of input has now emerged as a major factor in GnRH secretion. Hypothalamic neurons containing kisspeptins, members of the RFamide family of peptides that contain the Arg-Phe-NH2 sequence at their terminus project to the GnRH neurons. Kisspeptin released from the synapse binds to Kiss1 receptors, providing what now appears is the most powerful endogenous stimulus for GnRH secretion.


These systems are of great interest to both physiologists and neuroscientists for a variety of reasons.

Second, the neurons of the neuroendocrine system 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. Hence, neuroendocrine neurons are good "model systems" for studying general questions, like "how does a neuron regulate the synthesis, packaging, and secretion of its product?" and "how is information encoded in electrical activity?"

The scope of neuroendocrinologyEdit

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, whose steroids, in turn, influence the brain, as do corticosteroids secreted from the adrenal gland under the influence of ACTH. The study of these feedbacks became 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 that appeared to serve 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.

Neuroendocrinology is also used as an integral part of understanding and treating neurobiological brain disorders. One example is the augmentation of the treatment of mood symptoms with thyroid hormone. [1] Another is the finding of a Transthyretin (Thyroxine transport) problem in the cerebrospinal fluid (CSF) of some patients diagnosed with schizophrenia.[2]


Neuro-endocrine societiesEdit

Neuroendocrine JournalsEdit


See alsoEdit


ReferencesEdit

  1. Identifying hypothyroidism’s psychiatric presentations (November 2006 edition of Current Psychiatry Online)
  2. Huang JT, Leweke FM, Oxley D, et al (2006). Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis. PLoS Med. 3 (11): e428.

Further readingEdit

Key textsEdit

BooksEdit

  • Lovejoy, DA (2005)Neuroendocrinology: An Integrative Approach. Wiley.ISBN 0470844329

PapersEdit

Additional materialEdit

BooksEdit

PapersEdit

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