Disease relevance of POMC

• We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH, and the CRH type 1 receptor (CRHR(1)) shortly before birth and during chronic placental insufficiency [1].
• We conclude that in response to prolonged hypoxemia, there is differential regulation of POMC mRNA levels in the pars distalis and pars intermedia of the pituitary in fetal sheep [2].
• In contrast, the elevated basal levels of POMC peptides in the HPD animals were not significantly increased by the hypoglycemia, but a significant elevation of plasma cortisol was seen [3].
• Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus [4].

High impact information on POMC

• It may also act in a paracrine fashion to promote placental POMC gene expression [5].
• In fetuses subjected to experimental induction of placental restriction, the prepartum surge in fetal cortisol is exaggerated, whereas pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs nonresponsive to CRH [1].
• This study is the first to demonstrate subpopulations of corticotrophs in the fetal sheep pituitary that differentially express POMC, ACTH, and CRHR(1) and the separate effects of gestational age and placental restriction on these subpopulations of corticotrophs [1].
• The prepartum surge in fetal plasma cortisol is essential for the normal timing of parturition in sheep and may result from an increase in the ratio of ACTH to proopiomelanocortin (POMC) in the fetal circulation [1].
• Glucose infusion increased mRNA expression for POMC, but not for the anorectic neuropeptide CART, or the orexigenic neuropeptides NPY and AGRP, in the arcuate nucleus of the fetal hypothalamus [6].

Chemical compound and disease context of POMC

• The increase in POMC mRNA levels in the pars distalis at 48 h of hypoxemia, despite a rise in plasma cortisol and without a change in corticosteroid-binding globulin, suggests altered regulation of HPA function at this time [2].

Biological context of POMC

• These observations differ from the rat, in which CRF is the most potent of the ACTH-releasing factors and the only ACTH secretagogue which stimulates POMC gene expression and biosynthesis [7].
• The current study sought to define the effects of altered adiposity on the expression of genes for neuropeptide Y (NPY), POMC, enkephalin (ENK), and melanin-concentrating hormone (MCH) [8].
• A 295 base pair portion of the ovine POMC gene was isolated using polymerase chain reaction and sequenced [7].
• Gene expression was decreased for cocaine- and amphetamine-regulated transcript (CART) in the ARC and VMH and for proopiomelanocortin in ARC during lactation [9].
• Finally, we report that increase in corticotrope POMC transcripts during late gestation in the inferior AP requires an intact PVN [10].

Anatomical context of POMC

• In conclusion, the fetal PVN is necessary for sustaining adequate anterior pituitary processing of POMC to ACTH and ACTH release needed for maturing the adrenal cortex in the sheep fetus [11].
• CART mRNA was localised in the arcuate nucleus (ARC), paraventricular nucleus, median eminence and ventromedial hypothalamic nucleus, and extensive co-localisation with POMC mRNA was demonstrated in the ARC [12].
• Our results demonstrate that this short E2 treatment significantly decreased both the mean number of silver grains per POMC-containing cell (35%) and the mean number of POMC-cells (38%) in the ovine infundibular nucleus, whereas the treatment had no effect on preproNPY mRNA expression [13].
• Proopiomelanocortin processing in the anterior pituitary of the ovine fetus after lesion of the hypothalamic paraventricular nucleus [11].
• Total RNA was extracted from these tissues and dot blotted onto nitrocellulose membranes for hybridization with a DNA probe complementary to the POMC mRNA [14].

Associations of POMC with chemical compounds

• The present studies were undertaken to determine if ovine POMC gene expression, unlike the rat POMC gene, is stimulated by AVP via the protein kinase C pathway [7].
• Influence of food restriction on neuropeptide-Y, proopiomelanocortin, and luteinizing hormone-releasing hormone gene expression in sheep hypothalami [15].
• Early decrease of proopiomelanocortin but not neuropeptide Y mRNA expression in the mediobasal hypothalamus of the ewe, during the estradiol-induced preovulatory LH surge [13].
• After the cloning of the ovine cDNA sequences and using in situ hybridization, hypothalamic proopiomelanocortin (POMC), and preproneuropeptide Y (preproNPY) mRNA expression was studied in ovariectomized ewes that received a sequential treatment of progesterone and E2 [13].
• Total RNA was prepared by the guanidium isothiocyanate-cesium chloride method and subjected to Northern analysis using specific cDNA probes to CRH and POMC [16].

Regulatory relationships of POMC

• Cortisol attenuated (p < 0.05) the neuropeptide-induced increases in POMC mRNA, though AVP-stimulated POMC mRNA levels were significantly higher than in cells treated with cortisol alone [17].

Other interactions of POMC

• The HPD lesion effectively destroyed the entire median eminence [no nerve terminals immunostained for tyrosine hydroxylase (TH) and gonadotropin-releasing hormone] and the adjacent arcuate nucleus (no perikarya immunostained for proopiomelanocortin or TH, and no cells expressed neuropeptide Y mRNA) [18].
• No differences in the percentage of POMC cells containing CRF1 receptor hybridization signal were observed in the superior region of the anterior pituitary between PVN-Lx (89+/-8%) and SHAM (87+/-9%) [19].
• In the neurointermediate lobe, POMC, PC1, and PC2 were ubiquitously expressed at all ages [20].
• Total RNA was subjected to Northern analysis using specific complementary DNA probes to CRH and POMC, and specific message was normalized to actin mRNA content in each individual sample [21].
• AVP treatment significantly increased the percentage of irACTH- and POMC-secreting cells in nonpregnant, but not in pregnant, ewes [22].

Analytical, diagnostic and therapeutic context of POMC

• Ovine POMC messenger RNA (mRNA) levels were quantitated using this partial complementary DNA clone in a solution hybridization/nuclease protection assay with cytoplasmic RNA from sheep anterior pituitary primary cultures which had been treated with various combinations of ACTH secretagogues or with glucocorticoids for 18 h [7].
• Adrenalectomy in fetal sheep significantly increased expression of CRH and POMC [16].
• We used two-site immunoradiometric assays to separately measure high mol wt ACTH precursors (POMC and pro-ACTH) and ACTH-(1-39) in plasma of fetal sheep with chronic arterial and venous catheters [23].
• The ratio of anterior pituitary POMC mRNA:18 S ribosomal RNA was also lower (p < 0.05) in the PR group (0.49 +/- 0.05) when compared with the control group (0.80 +/- 0.12) after 140 d of gestation [24].
• As measured by Western blot analysis, the proportion of ACTH(1-39) to POMC and pro-ACTH (22 kDa) also increased significantly with developmental age [25].

References