Disease relevance of Pomc

• CONCLUSIONS/INTERPRETATION: This study demonstrates that targeted Pomc gene therapy in the hypothalamus reduces body weight and visceral adiposity, and improves glucose and fat metabolism in aged obese rats [1].
• AIMS/HYPOTHESIS: Age-related obesity is associated with impaired hypothalamic pro-opiomelanocortin (Pomc) gene expression [1].
• METHODS: Recombinant adeno-associated virus (rAAV) encoding Pomc (rAAV-Pomc) or control vector was delivered bilaterally into the basomedial hypothalamus of aged obese rats with coordinates targeting the arcuate nucleus [1].
• The effect of uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia [2].
• NPY infusion produced hypogonadism and hyposomatotropism in the face of markedly elevated plasma leptin levels and an important reduction in hypothalamic POMC synthesis [3].

Psychiatry related information on Pomc

• Food deprivation significantly decreased the arcuate POMC mRNA level in both groups [4].
• Products of the proopiomelanocortin (POMC) gene are known to affect feeding behavior, and POMC neurons share a similar distribution with leptin receptor mRNA in the arcuate nucleus [5].

High impact information on Pomc

• It has also been found to cleave some Phe and Arg bonds in various substrates such as beta-lipotropin (beta-LPH), adrenocorticotropin (ACTH), pro-opiomelanocortin (POMC) and substance P [6].
• Dexamethasone administration to intact or adrenalectomized rats results in the rapid (within 30 minutes) disappearance of silver grains over the nuclei of corticotrophs in the anterior lobe, suggesting that POMC gene transcription had been inhibited [7].
• Regulation of pro-opiomelanocortin gene transcription in individual cell nuclei [7].
• The testicular POMC messenger RNA is comparable in length to amygdala and midbrain POMC messenger RNA and appears to be at least 200 nucleotides shorter than POMC messenger RNA found in the hypothalamus and anterior and intermediate lobes of the pituitary gland [8].
• These results suggest that local synthesis of POMC occurs in the testis [8].

Chemical compound and disease context of Pomc

• Propylthiouracil (PTU)-induced hypothyroidism caused a significant reduction in CRH gene transcripts in the paraventricular nucleus of male rats, with a concomitant decrease in both POMC gene expression in the anterior pituitary gland and circulating corticosterone [9].
• In the present study we examined the effects of central administration of EP on ACTH secretion and gene expression of both CRF in the hypothalamus and POMC in the anterior pituitary gland (AP) during basal and insulin-induced hypoglycemia in pentobarbital-anesthetized rats [10].
• The present study assessed the effects of dexamethasone (DEX) on these hormones, and on ACTH and pituitary proopiomelanocortin (POMC) and corticotropin-releasing hormone receptor-1 (CRHR1) mRNA expression, during a common metabolic stress - neonatal hypoxia [11].
• D-2 dopamine receptor-mediated inhibition of pro-opiomelanocortin synthesis in rat intermediate lobe. Abolition by pertussis toxin or activators of adenylate cyclase [12].
• The potency of pertussis toxin in abolishing the dopaminergic inhibition of POMC synthesis corresponded to its potency in abolishing the D-2 dopaminergic inhibition of adenylate cyclase activity [12].

Biological context of Pomc

• Pomc gene delivery decreased visceral adiposity and induced uncoupling protein 1 in brown adipose tissue in aged rats [1].
• Agonists for melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin (POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases food intake [2].
• Furthermore, changes in NPY and POMC agree with current models of food intake behavior, but they are opposite to their acute effects on peripheral energy metabolism and thermogenesis [13].
• The developmental dynamics of this cell population and its response to CRH in vitro in the rat suggest a relationship of these cells with the embryonic branching of the POMC and alphaGSU cell lineages and their mutually opposite developmental course during early postnatal life [14].
• Changes in expression of NPY, AgRP or POMC alone could not account for the diurnal changes in intake and their alteration by lactation [15].

Anatomical context of Pomc

• Using a punch technique, we detected the highest Pomc RNA level in the arcuate nucleus [1].
• The duration of increased gene expression of MC4R and POMC in the amygdala was more sustained than in the hypothalamus [16].
• POMC neurons are also found in the nucleus tractus solitarius (NTS), a region regulating satiety [17].
• Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area [18].
• Correspondingly, in these animals, CNTF failed to activate STAT3 phosphorylation in POMC neurons and to induce c-Fos expression in the paraventricular nucleus [19].

Associations of Pomc with chemical compounds

• Improved glucose metabolism and insulin sensitivity were observed on day 36 but not day 20 after Pomc gene delivery [1].
• Serum NEFA and triglyceride levels were also diminished by rAAV-Pomc treatment [1].
• We examined by means of RT-PCR and immunostaining whether glycoprotein hormone alpha-subunit (alphaGSU) could be coexpressed with proopiomelanocortin (POMC) in vivo and under pressure of CRH in vitro [14].
• In the first study effects of ADX and corticosterone replacement on POMC and AGRP expression were determined [20].
• Levels of transcripts for mRNA for both CRF and POMC were markedly reduced after the treatment, but there was a rapid return to control values for CRF mRNA within 18 h of steroid withdrawal [21].

Physical interactions of Pomc

• CRH-R mRNA decreased by 59% 5 h after injection of corticosterone (10 mg s.c.) and returned to basal levels by 18 h, a time when plasma corticosterone concentrations were still elevated, and CRH binding and POMC hnRNA were significantly reduced [22].
• Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription [23].

Regulatory relationships of Pomc

• Systemic administration of a specific anti-CRH antiserum inhibited the ACTH response to 5-HTP and fluoxetine and prevented the 5-HTP and fluoxetine-induced POMC mRNA response in the anterior pituitary lobe [24].
• Among these, a dense cluster of small neuropeptide-Y (NPY)-expressing neurons is located in its ventromedial subdivision and a pro-opiomelanocortin (POMC)-expressing neuron population in its ventrolateral part [25].
• These results suggest that alpha-MSH, a cleaved peptide from pro-opiomelanocortin of which synthesis is stimulated by leptin, may be the pivotal neuropeptide in the brain mediating the leptin's stimulatory influence on PRL secretion [26].
• The proportion of POMC neurones expressing MC3-R mRNA was significantly higher in the most rostral (43.5%) than in the most posterior part of the arcuate nucleus (8.2%) [27].
• We used double label in situ hybridization and computerized image analysis to test the hypothesis that POMC neurons coexpress the leptin receptor [5].

Other interactions of Pomc

• In fed animals, 47% of arcuate nucleus neurons containing NPY mRNA also contained Ob-Rb mRNA, compared with 79% of POMC neurons (P < 0.01) [28].
• Serotonergic stimulation of corticotropin-releasing hormone and pro-opiomelanocortin gene expression [24].
• By real-time polymerase chain reaction and in situ hybridisation, mRNA levels of neuropeptide Y, but not pro-opiomelanocortin and galanin-like peptide, were significantly increased in the ARC of GK rats at 11 weeks, but not 26 weeks [29].
• The ratio of hypothalamic Pomc to Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats, which is consistent with increased stimulation of central melanocortin signalling pathways [30].
• Arthritis induced a higher expression of POMC and IL-6 in the AP and a suppression of IL-1 beta mRNA during the 24-hour cycle which suggests the involvement of different regulatory mechanisms compared to normal conditions [31].

Analytical, diagnostic and therapeutic context of Pomc

• In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by 80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin signaling [2].
• Effects of adrenalectomy on AGRP, POMC, NPY and CART gene expression in the basal hypothalamus of fed and fasted rats [20].
• Here we analyse the co-expression of NPY and POMC/adrenocorticotropic hormone with the Y1-R and Y2-R in arcuate neurons using immunohistochemistry and in situ hybridization [25].
• ARC NPY and DMH galanin mRNAs increased following repeated immobilization, while ARC POMC mRNA decreased [32].
• Little is known about regulation of their production, and therefore the purpose of the present work was to describe the relationship between circulating corticosterone and the mRNA expression of proopiomelanocortin (POMC), IL-1 beta and IL-6 in the AP during a 24-hour cycle in normal rats and rats with acute adjuvant arthritis (AA) [31].

References