The arcuate nucleus of the hypothalamus (also known as ARH, ARC, or infundibular nucleus) is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

Cell populations

Neuroendocrine neurons

Different groups of arcuate nucleus neuroendocrine neurons secrete various types or combinations of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

s and neuropeptides, such as neuropeptide Y (NPY), gonadotropin-releasing hormone (GnRH), agouti-related peptide (AgRP), cocaine- and amphetamine-regulated transcript (CART), kisspeptin,

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

, substance P,

growth hormone–releasing hormone Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by #Nomenclature, several other names in its endogeny (biology), endogenous forms and as somatorelin (International Nonproprietary Name, INN) in its pharmaceutical, pharmace ...

(GHRH), neurokinin B (NKB), β-endorphin, melanocyte-stimulating hormone (MSH), and

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...

. Proopiomelanocortin (POMC) is a precursor

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

that is cleaved into MSH, ACTH, and β-endorphin and expressed in the arcuate nucleus. Groups of neuroendocrine neurons include: * TIDA neurons, or tuberoinfundibular dopamine neurons, are neurons that regulate the secretion of prolactin from the pituitary gland and release the neurotransmitter

. TIDA neurons have nerve endings in the median eminence that release

into the hypophysial portal blood. In lactating females, TIDA neurons are inhibited by the stimulus of suckling. Dopamine released from their nerve endings at the median eminence is transported to the anterior pituitary gland, where it regulates the secretion of prolactin. Dopamine inhibits prolactin secretion, so when the TIDA neurons are inhibited, there is increased secretion of prolactin, which stimulates lactogenesis (milk production). Prolactin acts in a short-loop negative feedback manner to decrease its levels by stimulating the release of dopamine. Dopaminergic neurons of the arcuate also inhibit the release of gonadotropin-releasing hormone, explaining in part why lactating (or otherwise hyperprolactinemic) women experience oligomenorrhea or amenorrhea (infrequency or absence of menses). * Kisspeptin/NKB neurons within the arcuate nucleus form synaptic inputs with TIDA neurons. These neurons express estrogen receptors and also coexpress neurokinin B in female rats. * GHRH neurons help to control growth hormone (GH) secretion in conjunction with somatostatin and NPY. * NPY/AgRP neurons and POMC/CART neurons make up two groups of neurons in the arcuate nucleus that are centrally involved in the neuroendocrine function of feeding. Medial neurons utilize NPY peptides as neurotransmitters to stimulate appetite, and lateral neurons utilize POMC/CART to inhibit appetite. NPY and POMC/CART neurons are sensitive to peripheral hormones such as leptin and insulin. POMC/CART neurons also secrete melanocyte-stimulating hormone, which suppresses appetite. * GnRH neurons have also been found. These neurons secrete GnRH and histamine. * There are also groups of neurons expressing NKB and dynorphin that help to control reproduction.

Centrally-projecting neurons

Other types of neurons have projection pathways from the arcuate nucleus to mediate different regions of the hypothalamus or to other regions outside of the hypothalamus. Projections of these neurons extend a long distance from the arcuate nucleus to the median eminence to influence the release of hormones from the pituitary gland. Neurons of the arcuate nucleus have intrahypothalamic projections for neuroendocrine circuitry. such as neural projections that influence feeding behavior project to the paraventricular nucleus of the hypothalamus (PVH), the dorsomedial hypothalamic nucleus (DMH, and the lateral hypothalamic area (LHA). Populations of neurons connect to the intermediate lobes of the pituitary gland, from the lateral division of the ARH to the neural and intermediate parts of the pituitary gland, and the caudal division of ARH to the median eminence. Groups of neurons that project elsewhere within the central nervous system include: * Centrally projecting neurons that contain neuropeptide Y (NPY),

agouti-related protein Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nu ...

(AGRP), and the inhibitory neurotransmitter GABA. These neurons, in the most ventromedial part of the nucleus, project strongly to the lateral hypothalamus and to the paraventricular nucleus of the hypothalamus, and are important in the regulation of

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regu ...

. When activated, these neurons can produce ravenous eating. These neurons are inhibited by

leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

, and peptide YY and activated by ghrelin. * Centrally projecting neurons that contain peptide products of pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). These neurons have widespread projections to many brain areas, including to all nuclei in the hypothalamus. These cells are important in the regulation of

, and, when activated, they inhibit feeding. These neurons are activated by circulating concentrations of

and

, and they are directly innervated and inhibited by the NPY neurons. POMC neurons that project to the medial preoptic nucleus are also involved in the regulation of sexual behavior in both males and females. The expression of POMC is regulated by gonadal steroids. The release of a POMC product, beta-endorphin is regulated by NPY. * Centrally projecting neurons that make somatostatin; the neurosecretory somatostatin neurons that regulate growth hormone secretion are a different population, located in the periventricular nucleus. * Feeding regulatory neurons also activate oxytocin-containing neurons of the periventricular nucleus (PVN), which projects to nucleus of

tractus solitarius The solitary tract (tractus solitarius, or fasciculus solitarius), is a compact fiber bundle that extends longitudinally through the posterolateral region of the medulla oblongata. The solitary tract is surrounded by the solitary nucleus, and des ...

in the

medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...

. * Others receive direct synaptic inputs from extra hypothalamic sites projecting into the amygdala, the hippocampus, and the entorhinal cortex.

Other neurons

Other cell populations include: * A small population of neurons that sensitive to ghrelin. The role of this population is not known; many neurons in the arcuate nucleus express receptors for ghrelin, but these are thought to respond mainly to blood-borne ghrelin. * The arcuate nucleus also contains a population of specialized ependymal cells, called tanycytes. * Astrocytes in the arcuate nucleus hold high capacity glucose transporters that function as nutrient sensors for appetite controlling neurons * The diverse and specialized collections of neurons reside within a special compartment with glial cells and have their own network of capillaries and a membrane of tanycytes that help create a blood brain barrier. Circulating or molecules such as hormones travel in the blood and can directly affect these neurons and their plasticity as evidence by adult neurogenesis.

References

Footnotes

* * * {{DEFAULTSORT:Arcuate Nucleus Hypothalamus Neuroendocrinology Human female endocrine system