Where is pomc produced

Learn more. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. POMC gene proopiomelanocortin. From Genetics Home Reference. Normal Function The POMC gene provides instructions for making a protein called proopiomelanocortin POMC , which is cut cleaved into smaller pieces called peptides that have different functions in the body.

More About This Health Condition. A role for beta-melanocyte-stimulating hormone in human body-weight regulation. Cell Metab. Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival.

Ann N Y Acad Sci. The natriuretic mechanism of Gamma-Melanocyte-Stimulating Hormone. Epub Feb It is clear that the arcuate nucleus to PVN circuit is fundamental in the transmission of the satiety message in the hypothalamus. This suggests that CRF acts downstream of the melanocortin system. These central effects of the melanocortins on the stress and thyroid axes suggest that POMC neurones may influence peripheral metabolism, which will in turn indirectly affect feeding behaviour.

Damage to the lateral hypothalamus inhibits feeding, reducing body weight [ ]. The lateral hypothalamus expresses leprb mRNA and is regulated by leptin throughout development [ ]. However, both mc3r and mc4r mRNA are located in the lateral hypothalamus Table 3 ; [ 90 , ] and there is immunoreactive evidence of both POMC and AGRP fibres projecting from the arcuate nucleus to the lateral hypothalamus Table 1 ; [ 93 ] , so the lack of response to the MSHs administered icv is perhaps surprising.

Orexin expressing cells are located in the lateral, dorsal and perifornical nuclei. They innervate the arcuate nucleus, preoptic area, paraventricular nucleus of the thalamus, septal nuclei, locus coeruleus and DMX in the brainstem, as measured immunocytochemically. Microinjection of orexins into the arcuate nucleus, PVN and lateral hypothalamus stimulates feeding [ — ].

It is possible to measure the action potential of individual living arcuate POMC neurones in mouse brain slices, identified by GFP transgenic tagging. Using whole cell patch clamp recordings, orexin suppresses the spontaneous firing in these neurones, suggesting that its appetite enhancing effects include an effect in suppressing hypothalamic POMC neuronal activity [ ]. Lesioning experiments suggest that it has extensive projections to the PVN, particularly portions involved in autonomic control [ ].

These experiments also show that lesions of this nucleus produce hypophagia and reduce linear growth [ ]. Using techniques already described in this article, there is evidence of POMC projections from the arcuate nucleus to the DMH Table 1 ; [ 93 ] and both mc3r and mc4r mRNA are found in this nucleus Table 3 ; [ 90 , ]. Using a retrograde-labelled approach to measure axonal transport, there is evidence that some of these projections from the DMH to the PVN may be under the control of POMC neurones originating in the arcuate nucleus [ ].

The SON lies laterally in a bilateral position at the base of the hypothalamus. The SON and the mPVN contain oxytocin and vasopressin cells, which project to the posterior pituitary, where these hormones are released [ 3 , ].

CCK co-expression in oxytocin neurones in the SON occurs in rats on a normal diet only, rather than a high fat diet [ ]. The VMH has no known neuroendocrine projections [ 42 ], but lesioning experiments show that it is involved in feeding behaviour in the rat [ ]. The projection from the arcuate nucleus to the VMH is very sparse and very few of these fibres are POMC neurones on immunocytochemistry Table 1 ; [ 93 ]. Despite this, mc3r and mc4r mRNA are abundant Table 3 ; [ 90 , ].

TrkB -deficient humans show learning difficulties and severe obesity [ ]. Cafeteria diet-induced obese rats have been shown to have increased somatostatin protein content and gene expression in the periventricular nucleus [ ]. Using a double-labelled immunocytochemical approach, arcuate nucleus POMC neurones have been shown to project to the majority of somatostatin perikarya in the periventricular nucleus [ ].

This implies that the effects of somatostatin on growth and body composition are under the influence of the melanocortins [ ]. Similarly, somatostatin receptors are located on POMC arcuate nucleus neurones, suggesting bidirectional communication [ ]. These observations link the hypothalamic functions of appetite and growth regulation. There is immunocytochemical evidence that the nucleus accumbens of the forebrain receives both POMC and AgRP projections from the arcuate nucleus Table 1 ; [ 93 ] , as well as a dopamine projection which mediates the reinforcing effects of stimulants, like cocaine, amphetamine, nicotine and caffeine [ — ].

Microinjection of muscimol, a GABA A receptor agonist, into the nucleus accumbens, increases feeding. This may be a mechanism for the appetite modulating effects of cocaine, amphetamine, nicotine and caffeine. The amygdala, located in the mid-temporal lobe, assigns emotional significance to sensory information, such as fear-related responses [ ]. It receives auditory and other efferents from the thalamus, cortex and hypothalamus.

In turn, it projects to brainstem and hypothalamic regions that regulate autonomic, endocrine and feeding responses [ ]. The release of CRF and bombesin-like peptides in the amygdala is markedly increased by both stress and feeding [ ]. Polygenic traits, such as obesity, result from complex combinations of multiple contributing genes [ ], environmental factors [ ], or gene-environment interactions [ ]. However, several rare monogenic human obesity syndromes have recently been described.

All of these syndromes are associated with hyperphagia. The last three of these gene defects produce altered protein products involved in POMC neuronal transmission Figure 1.

The other three are key factors interacting with the central melanocortin pathway. Also, when the melanocortin antagonist AgRP is mutated in either rodents or humans, it leads to thinness [ 53 — 55 ]. Thus, there is considerable human and murine genetic evidence for the involvement of the central melanocortin pathways in the control of appetite [ 7 ]. Could genetic variation in this system and that of related interacting molecules be part of the polygenic tendency to obesity in humans [ 7 , 40 , 41 , 44 — 46 , , , ]?

POMC heterozygosity has also been found to correlate with obesity in mice and humans, to a lesser extent than the homozygous state [ 9 , ]. In summary, the likely model for the melanocortin regulation of feeding is that the AgRP signal in the arcuate nucleus fluctuates to modulate a more constant POMC signal [ 57 , 59 ], which is a function of the relatively steady hormonal level of leptin [ 49 ]. POMC products may be released differentially in the different hypothalamic and extra-hypothalamic sites involved with feeding in the CNS [ 42 ], which could lead to subtle variations in the anorexic signal being transmitted.

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John's College, University of Cambridge is gratefully acknowledged. You can also search for this author in PubMed Google Scholar. Correspondence to George WM Millington.