Disease relevance of POMC

• This reduction in POMC message is consistent with the onset of obesity in the animals [1].
• We hypothesize that the POMC melanocortin pathway provides a mechanistic basis for the observed effects of sulfur mustard on body weight [1].

High impact information on POMC

• This establishes that at least some POMC is packaged into secretory granules before its proteolytic cleavage [2].
• The SP6 polymerase/promoter system was used to synthesize porcine pro-opiomelanocortin mRNAs with nucleotide sequence deletions in the 5'- as well as 3'-untranslated and coding regions [3].
• Analysis of pro-opiomelanocortin-related material in COS-1 cell extracts and culture medium revealed that these cells synthesize and secrete constitutively pro-opiomelanocortin without further processing into its mature hormones [4].
• Transient expression of the pro-opiomelanocortin cDNA was observed between 48 and 70 h after transfection [4].
• Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal [5].

Chemical compound and disease context of POMC

• Decrease in brain POMC mRNA expression and onset of obesity in guinea pigs exposed to 2-chloroethyl ethyl sulfide, a mustard analogue [1].

Biological context of POMC

• We have determined the nucleotide sequences of the 5' noncoding regions and the regions encoding the first 56 amino acids of rat and porcine pro-opiomelanocortin (POMC) mRNA [6].
• The differences between the nucleotide and amino acid sequences of porcine POMC found hitherto may be attributable to strain differences [7].
• Proopiomelanocortin (POMC) mRNA expression: distribution and region-specific down-regulation by chronic morphine in female guinea pig hypothalamus [8].
• In the present study, developmental changes in gene expression of the Ob-Rl, preproorexin, proopiomelanocortin (POMC), corticotropin releasing factor (CRF), somatostatin, and GnRH in the hypothalamus was studied [9].
• The porcine POMC cDNA was inserted downstream from the late promoter of an SV40-derived expression vector and co-transfected in NIH 3T3 cells with a marker plasmid carrying the neomycin resistance gene [10].

Anatomical context of POMC

• The existence of heterogeneous molecular species of pro-opiomelanocortin (POMC) has been reported and it has been inferred that this explains the distinct release patterns of POMC-derived peptide hormones by the anterior and intermediate lobes of the pituitary gland [7].
• POMC mRNA was localized to the arcuate nucleus (Arc) and median eminence (ME) of the medial basal hypothalamus [8].
• These data suggest that both lung and thyroid gland synthesize POMC, which in normal tissue is usually predominantly processed to species other than ACTH and beta EP [11].
• Localization of proopiomelanocortin (POMC) immunoreactive neurons in the forebrain of the pig [12].
• Intracellular accumulation of POMC was not observed in NIH 3T3 fibroblasts [13].

Associations of POMC with chemical compounds

• The ATP-sensitive potassium channel opener diazoxide also induced an outward K(+) current (maximum of 18.7 +/- 2.2 pA) in the majority (92%) of POMC neurons with an EC(50) of 61 micro M [5].
• This pharmacological and molecular profile suggested that POMC neurons might be sensitive to metabolic inhibition, and indeed, we found that their firing rate varied with changes in glucose concentrations [5].
• In addition, the selective micro -opioid receptor agonist DAMGO induced an outward current (maximum of 12.8 +/- 1.2 pA), which reversed at K(+) equilibrium potential (E(K+)), in the majority (85%) of POMC neurons with an EC(50) of 102 nM [5].
• Estrogen rapidly uncouples mu-opioid receptors from G protein-gated inwardly-rectifying K(+) (GIRK) channels in POMC neurons and GABA(B) receptors from GIRK channels in dopamine neurons as manifested by a reduction in the potency of mu-opioid and GABA(B) receptor agonists to hyperpolarize their respective cells [14].
• These findings indicate a richly complex yet coordinated steroid modulation of K(+) channel activity in hypothalamic (POMC, dopamine, GABA, GnRH) neurons that are involved in regulating numerous homeostatic functions [14].

Other interactions of POMC

• However, HPA axis seems not to be fully developed in Day 77-fetuses because fetal pituitary CRHR1 and POMC mRNA expression was low in most of the fetuses [15].
• The hypothalamus, pituitary gland, adrenal glands, and liver were immediately obtained to determine the amounts of corticotropin-releasing hormone (CRH), beta-endorphin, and mRNA for pro-opiomelanocorticotropin (POMC), the ACTH receptor (ACTH-R), and insulin-like growth factor I (IGF-I) [16].
• Gene expression for PENK occurred in the caudate putamen (CPu), for POMC in the mediobasal hypothalamus (MBH) and for prolactin and POMC in the hypophysis [17].

Analytical, diagnostic and therapeutic context of POMC

• The POMC cDNAs were obtained using immunoscreening (anterior lobe) and the polymerase chain reaction (intermediate lobe), and their nucleotide sequences determined [7].
• Sequence analysis of the cDNA inserts revealed the complete structure of the porcine pro-opiomelanocortin mRNA [18].
• Steady-state analysis of acid extracts of dorsal caudal medulla from rat and guinea pig CNS by gel filtration chromatography and radioimmunoassay indicated that in both species the major POMC-related end products are alpha-MSH-sized material and beta-endorphin-sized [19].
• The expression of POMC mRNA were investigated using in situ hybridization histochemistry with a guinea pig specific 35S-labeled cRNA probe in hypothalamic tissue sections [8].
• Protein sequence analysis revealed that one of the PIF peptides was Trp-Cys-Leu-Glu-Ser-Ser-Gln-Cys-Gln-Asp-Leu-Ser-Thr-Glu-Ser-Asn-Leu-Leu- Ala-Cys - Ile-Arg-Ala-Cys-Lys-Pro, identical to residues 27-52 of the N-terminal region of the proopiomelanocortin (POMC) precursor (corresponding to amino acids 1-26 of the 16-kDa fragment) [20].

References