Neuroendocrinology

Neuroendocrinology is the study of the interaction between the nervous system and the endocrine system, including the biological features of the cells involved, and how they communicate. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. 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.

The neuroendocrine system is the mechanism by which the hypothalamus maintains homeostasis, regulating reproduction, metabolism, eating and drinking behaviour, energy utilization, osmolarity and blood pressure.

Neuroendocrine system

Hypothalamus

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 (also called anti-diuretic hormone), the two peptide hormones of the posterior pituitary gland (the neurohypophysis), are secreted from the nerve endings of magnocellular neuroendocrine cells into the systemic circulation. The cell bodies of the 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, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, and growth hormone) remains under the control of the hypothalamus. The hypothalamus controls the anterior pituitary gland via releasing factors and release-inhibiting factors; these are blood-borne substances [author means via bloodstream and not by the lymphatic system nor air, nor any other modes of transport] 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 anterior pituitary, 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.

The neuroendocrine systems control reproduction^[1] in all its aspects, from bonding to sexual behaviour. They control spermatogenesis and the ovarian cycle, parturition, lactation, and maternal behaviour. They control the body's response to stress^[2] and infection.^[3] They regulate the body's metabolism, influencing eating and drinking behaviour, and influence how energy intake is utilised, that is, how fat is metabolised.^[4] They influence and regulate mood,^[5] body fluid and electrolyte homeostasis,^[6] and blood pressure.^[7]

The neurons of the neuroendocrine system are large; they are mini factories for producing secretory products; their nerve terminals 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?"[It appears that this is a primary source observation.]

Pituitary gland

The pituitary gland is divided into two sections: the anterior pituitary and the posterior pituitary. The hypothalamus controls the anterior pituitary's hormone secretion by sending trophic hormones down the hypothalamohypophysial portal system. For example, thyrotropin-releasing hormone stimulates the secretion of thyroid-stimulating hormone by the anterior pituitary.

The posterior pituitary is innervated by the hypothalamus; the hormones oxytocin and vasopressin are synthesized by neuroendocrine cells in the hypothalamus and stored at the nerves' ends in the posterior pituitary. They are secreted directly into systemic circulation by the hypothalamic neurons.

History

Pioneers

Ernst and Berta Scharrer,^[8] of the University of Munich the Albert Einstein College of Medicine are credited as co-founders the field of neuroendocrinology with their initial observations and proposals in 1945 concerning neuropeptides.

Geoffrey Harris^[9] is considered by many to be the "father" of neuroendocrinology. 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 hormones 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; GnRH (also called luteinizing hormone-releasing hormone) stimulates the secretion of luteinizing hormone and follicle-stimulating hormone.

Roger Guillemin,^[10] 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.^[11]

Modern scope

Today, neuroendocrinology embraces a wide range of topics that arose directly or indirectly from the core concept of neuroendocrine neurons. Neuroendocrine neurons control the gonads, whose steroids, in turn, influence the brain, as do corticosteroids secreted from the adrenal gland under the influence of adrenocorticotrophic hormone. 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.^[12] 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.^[13] Another is the finding of a transthyretin (thyroxine transport) problem in the cerebrospinal fluid of some patients diagnosed with schizophrenia.^[14]

See also

• Molecular neuroscience
• Neurochemistry
• Neuroendocrine
• Neuropharmacology
• Neurobiological brain disorder

References

1. Blázquez, M.; Bosma, P.T.; Fraser, E.J.; Van Look, K.J.W.; Trudeau, V.L. (June 1998). "Fish as models for the neuroendocrine regulation of reproduction and growth". Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology 119 (3): 345–364. doi:10.1016/S0742-8413(98)00023-1. ISSN 0742-8413. PMID 9827007. Cite uses deprecated parameter |coauthors= (help)
2. Ratka, Anna; Sutanto, Winardi; Bloemers, Margreet; de Kloet, Ronald (1989). "On the Role of Brain Mineralocorticoid (Type I) and Glucocorticoid (Type II) Receptors in Neuroendocrine Regulation". Neuroendocrinology 50 (2): 117–123. doi:10.1159/000125210. ISSN 0028-3835.
3. Webster, Jeanette I; Tonelli, Leonardo; Sternberg, Esther M (2002). "Neuroendocrine regulation of immunity" (PDF). Annual Review of Immunology 20: 125–163. doi:10.1146/annurev.immunol.20.082401.104914. ISSN 0732-0582. PMID 11861600.
4. McMinn, J. E.; Baskin, D. G.; Schwartz, M. W. (2000). "Neuroendocrine mechanisms regulating food intake and body weight". Obesity Reviews 1 (1): 37–46. doi:10.1046/j.1467-789x.2000.00007.x. ISSN 1467-789X. PMID 12119644.
5. Davidson, Richard J; Lewis, David A; Alloy, Lauren B; Amaral, David G; Bush, George; Cohen, Jonathan D; Drevets, Wayne C; Farah, Martha J; Kagan, Jerome; McClelland, Jay L; Nolen-Hoeksema, Susan; Peterson, Bradley S (15 September 2002). "Neural and behavioral substrates of mood and mood regulation" (PDF). Biological Psychiatry 52 (6): 478–502. doi:10.1016/S0006-3223(02)01458-0. ISSN 0006-3223. PMID 12361665. Cite uses deprecated parameter |coauthors= (help)
6. Antunes-Rodrigues, José; Castro, Margaret De; Elias, Lucila L. K.; Valença, Marcelo M.; McCANN, Samuel M. (1 January 2004). "Neuroendocrine Control of Body Fluid Metabolism". Physiological Reviews 84 (1): 169–208. doi:10.1152/physrev.00017.2003. ISSN 1522-1210. PMID 14715914.
7. Lenkei, Z; Corvol, P; Llorens-Cortes, C (May 1995). "The angiotensin receptor subtype AT1A predominates in rat forebrain areas involved in blood pressure, body fluid homeostasis and neuroendocrine control". Molecular Brain Research 30 (1): 53–60. doi:10.1016/0169-328X(94)00272-G. ISSN 0169-328X. PMID 7609644.
8. Scharrer, Ernst; Scharrer, Berta (1 January 1945). "Neurosecretion". Physiological Reviews 25 (1): 171–181. ISSN 1522-1210.
9. Raisman, G (1997). "An urge to explain the incomprehensible: Geoffrey Harris and the discovery of the neural control of the pituitary gland" (PDF). Annual Review of Neuroscience 20: 533–566. doi:10.1146/annurev.neuro.20.1.533. ISSN 0147-006X. PMID 9056724.
10. Guillemin, Roger; Schally, Andrew V.; Lipscomb, Harry S.; Andersen, Richard N.; Long, John M. (1 April 1962). "On the Presence in Hog Hypothalamus of (β-Corticotropin Releasing Factor, α- and (β-Melanocyte Stimulating Hormones, Adrenocorticotropin, Lysine-Vasopressin and Oxytocin". Endocrinology 70 (4): 471–477. doi:10.1210/endo-70-4-471. ISSN 1945-7170. PMID 13902822.
11. Berczi, Istvan (2010). "Dr Andor Szentivanyi Memorial". University of Manitoba. (Warning: automatic background music)
12. Misler, Stanley (1 September 2009). "Unifying concepts in stimulus-secretion coupling in endocrine cells and some implications for therapeutics". Advances in Physiology Education 33 (3): 175–186. doi:10.1152/advan.90213.2008. ISSN 1522-1229. PMID 19745043. Retrieved 12 December 2013.
13. Geracioti TD (2006). "Identifying Hypothyroidism's Psychiatric Presentations". Current Psychiatry 5 (11): 98–117.
14. Huang, Jeffrey T-J; Leweke, F Markus; Oxley, David; Wang, Lan; Harris, Nathan; Koethe, Dagmar; Gerth, Christoph W; Nolden, Brit M; Gross, Sonja; Schreiber, Daniela; Reed, Benjamin; Bahn, Sabine (November 2006). "Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis". PLOS Medicine 3 (11): e428. doi:10.1371/journal.pmed.0030428. ISSN 1549-1676. PMC 1630717. PMID 17090210. Cite uses deprecated parameter |coauthors= (help)

• Millington G, Buckingham JC (1992). "Thymic peptides and neuroendocrine-immune communication". J. Endocrinol. 133 (2): 163–8. doi:10.1677/joe.0.1330163. PMID 1613418.