Arcuate nucleus

The arcuate 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 populations of neurons, including:

• Neuroendocrine neurons with nerve endings in the median eminence, which release dopamine into the hypophysial portal blood. These are sometimes called the "tuberoinfundibular dopamine" (TIDA) neurons. 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).

• Neuroendocrine neurons, mainly in the ventrolateral part of the nucleus, that make growth hormone-releasing hormone (GHRH). Like the TIDA neurons, these neurons have nerve endings in the median eminence. GHRH released into the hypophysial portal blood is transported to the anterior pituitary gland, where it regulates the secretion of growth hormone; GHRH stimulates growth hormone secretion. These neurons are inhibited by somatostatin. The reciprocal relationship between the electrical activity of GHRH neurons and that of somatostatin neurons leads to pulsatile secretion of growth hormone, a pattern of secretion that is important for its biological effectiveness.

• Centrally-projecting neurons that contain neuropeptide Y (NPY), agouti-related protein (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. The expression of NPY and AgRP is stronly increased after a period of fasting, and when activated, these neurons can produce ravenous eating when food is available. These neurons are regulated by circulating concentrations of leptin and ghrelin. Selectively targetted destruction of these neurons leads to severe loss of appetite in experimental animals.

• Centrally-projecting neurons that contain peptide products of pro-opiomelanocortin (POMC), and cocaine-and-amphetamine-regulating transcript (CART). These neurons have widespread projections to many brain areas, including to all nuclei in the hypothalamus. These cells are also important in the regulation of appetite, and, when activated, they inhibit feeding. These neurons are also regulated by circulating concentrations of leptin and ghrelin, and they are directly innervated 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.

• A small population of neurons that synthesise ghrelin. The role of this population is not known; many neurons in the arcuate nucleus express receptors for ghrelin, but these are thought to be respond mainly to blood-borne ghrelin.

The arcuate nucleus also contains a population of specialized astrocytes, called tanycytes.

References

• Bouret SG, Simerly RB (2006) Developmental programming of hypothalamic feeding circuits.Clin Genet 70:295-301 PMID 16965320
• van den Top M, Spanswick D (2006) Integration of metabolic stimuli in the hypothalamic arcuate nucleus. Prog Brain Res 153:141-54 PMID 16876573
• Elmquist JK, et al 2005 Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol 493:63-71 PMID 16254991
• Cone RD (2005) Anatomy and regulation of the central melanocortin system.

Nat Neurosci 8:571-8 PMID 15856065

• Cone RD, et al (2001) The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 25 Suppl 5:S63-7 PMID 11840218
• Voogt JL et al (2001) Regulation of prolactin secretion during pregnancy and lactation. Prog Brain Res 133:173-85 PMID 11589129
• Sawchenko PE (1998) Toward a new neurobiology of energy balance, appetite, and obesity: the anatomists weigh in. J Comp Neurol 402:435-41 PMID 9862319
• Bluet-Pajot MT et al (1998) Hypothalamic and hypophyseal regulation of growth hormone secretion. Cell Mol Neurobiol 18:101-23 PMID 9524732

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