Neuroendocrinology is the study of the extensive interactions between the nervous system and the endocrine system, including the biological features of the cells that participate, and how they functionally communicate. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.
Contents |
Ernst and Berta Scharrer (1906-1995), of the University of Munich, and a professor at the Albert Einstein College of Medicine co-founded the field of neuroendocrinology with their initial observations and proposals concerning neuropeptides.
Geoffrey Harris[1] (1913-1971) is considered by many to be the "father" of neuroendocrinology. Geoffrey Harris, the Dr. Lee's Professor of Anatomy at Oxford University 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, a medical student of Faculté de Médecine of Lyon and Andrew W. Schally of Tulane University 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 of the University of South Florida and Geza Filipp wrote the world's first research paper showing how neural control of immunity takes place through the hypothalamus.[2]
The endocrine system consists of numerous glands throughout the body that produce and secrete hormones of diverse chemical structure, including peptides, steroids, and neuroamines. Collectively, hormones regulate many physiological processes.
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.
These systems are of great interest to both physiologists and neuroscientists for a variety of reasons. First, neuroendocrine systems 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 body's response to stress and infection. They regulate the body's metabolism, influencing eating and drinking behaviour, and influence how energy intake is utilised, that is, how fat is metabolized. They influence and regulate mood, body fluid and electrolyte homeostasis, and blood pressure. Therefore, essential in gaining understanding of the issues at the core of many of today's health concerns is to understand the neuroendocrine system.
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?"
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.[3] Another is the finding of a Transthyretin (Thyroxine transport) problem in the cerebrospinal fluid (CSF) of some patients diagnosed with schizophrenia.[4]
|
|||||||||||||