Proopiomelanocortin Synthesis and Cell‐Specific Processing

Mains, Richard E.; Eipper, Betty A.

doi:10.1002/cphy.cp070405

Cited by 4 publications

(5 citation statements)

References 202 publications

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“…There was an overall decrease (time, p < 0.05) in POMC expression by 7 days postpartum driven mainly by the response to CON. These longitudinal changes in POMC mRNA expression are likely of physiological significance and seem to agree with the half‐life of the transcript which in non‐ruminant pituitary has been measured in days (Mains and Eipper, 2011). Because murine liver expresses POMC at much lower level than the central nervous system (Liu et al., 2011), it is unknown whether mRNA half‐life is similar across tissues.…”

Section: Resultssupporting

confidence: 80%

“…Furthermore, negative energy balance because of fasting has been associated with lower POMC mRNA in hypothalamic neurons, a response associated with lower leptin (Korner et al., 2001). The negative correlation between POMC and NEFA may not be due to NEFA per se, but rather because of other stimuli such as glucocorticoids (Mains and Eipper, 2011). The fact that POMC also is regulated by post‐translational modifications (Millington, 2007) complicates the interpretation of mRNA expression data.…”

Section: Resultsmentioning

confidence: 99%

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Endocannabinoid system and proopiomelanocortin gene expression in peripartal bovine liver in response to prepartal plane of nutrition

Khan

Graugnard

Loor

2011

Animal Physiology Nutrition

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Endocannabinoids are fatty acid amides (FAE; oleoylethanolamide and anandamide) which have orexigenic, anorexigenic or anti-inflammatory properties. We examined mRNA expression via qPCR of endocannabinoid receptors (CNR1 and CNR2), enzymes that synthesize FAE (HRASLS5 and N-acyl phosphatidylethanolamine phospholipase D), enzymes that degrade FAE [fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA) and monoglyceride lipase (MGLL)], and the hormone precursor proopiomelanocortin (POMC) in liver at -14, 7, 14 and 30 days around parturition from cows fed with a control (CON; NE(L) = 1.34 Mcal/kg) or moderate-energy (OVER; NE(L) = 1.62 Mcal/kg) diet during the dry period. Expression of CNR2 and POMC was greater at 7 days in cows fed with OVER because of a decrease in expression between -14 and 7 days in cows fed with CON. Cows fed with CON had an increase in expression of FAAH, HRASLS5, NAA, MGLL and POMC between 7 and 14 days; for FAAH and HRASLS5, such response led to greater expression at 14 days vs. cows fed with OVER. Cows fed with OVER vs. CON had a approximately twofold increase in expression of MGLL between -14 and 7 days followed by a gradual decrease through 30 days at which point expression was still greater in OVER vs. CON. FAAH, MGLL and HRASLS5 were the most abundant genes measured. Expression of the hepatic endocannabinoid system and POMC was altered by plane of dietary energy prepartum particularly during the first 2-week postpartum. Such responses may play a role in the physiological adaptations to the onset of lactation, including energy balance and feed intake.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Endocannabinoid system and proopiomelanocortin gene expression in peripartal bovine liver in response to prepartal plane of nutrition

Khan

Graugnard

Loor

2011

Animal Physiology Nutrition

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“…Peptide precursors are known to be cleaved in a semi‐ordered fashion; for POMC, it has been suggested that PC1 first produces certain large intermediates and that PC2 then cleaves these intermediates to smaller products (reviewed in Mains and Eipper 2000). We and others have also noted order in the cleavage of PE, with the removal of peptide B occurring as a primary step (Mathis and Lindberg 1992; Rostovtsev and Wilson 1994).…”

Section: Discussionmentioning

confidence: 99%

Cleavage of recombinant proenkephalin and blockade mutants by prohormone convertases 1 and 2: an in vitro specificity study

Peinado

Johanning

et al. 2003

Journal of Neurochemistry

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Proenkephalin (PE) derived-peptides are thought to be generated predominantly through endoproteolytic cleavage by prohormone convertases 1 and 2 (PC1 and PC2). In order to compare cleavage site preferences of these convertases, we studied the processing of recombinant wild-type rat PE and of two mutant PEs by recombinant purified mouse PC1 and PC2. Western blot analyses of timed digestions showed that both mouse PC1 and PC2 were able to produce a variety of large and intermediate sized-peptides from wild-type PE as well as from the precursors mutated at initial blockade sites. PC2 exhibited a broader specificity against PE than PC1, generating a much greater number of peptide products. Mass spectrometric identification of cleavage products showed that PC2 appeared to be the principal enzyme involved in the generation of smaller active opioids. Both enzymes were able to cleave various KR-and KK-containing sites, but PC2 was also able to cleave efficiently at an RR-V site and a KK-M site not cleaved by PC1, suggesting the exclusion of large aliphatic residues at the P1¢ position in PC1 cleavage. Alternative cleavage sites were readily chosen by convertases in blockade mutants, confirming in vivo results that cleavages do not follow an obligatory order. Furthermore, glycosylated PE was less efficiently processed by PC2, indicating that glycosylation may serve as a mechanism to hinder processing.

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“…However, corticotrophs express mainly PC1 mRNA with low levels of PC2 mRNA, while melanotrophs express high levels of PC2 mRNA with appreciable PC1 mRNA levels (Seidah et al 1990, Day et al 1992. Since the specificity of PC1/3 and PC2 is not identical, processing of the POMC precursor differs greatly between corticotrophs and melanotrophs (Mains & Eipper 2000). In AL corticotrophs, POMC is processed mainly into adreno-corticotropic hormone (ACTH) and b-lipotropin as well as into lesser amounts of b-endorphin, while in NIL melanotrophs, POMC-derived peptides are cleaved to a variety of smaller bioactive peptides, such as a-melanocytestimulating hormone (a-MSH) and b-endorphin (Mains & Eipper 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Since the specificity of PC1/3 and PC2 is not identical, processing of the POMC precursor differs greatly between corticotrophs and melanotrophs (Mains & Eipper 2000). In AL corticotrophs, POMC is processed mainly into adreno-corticotropic hormone (ACTH) and b-lipotropin as well as into lesser amounts of b-endorphin, while in NIL melanotrophs, POMC-derived peptides are cleaved to a variety of smaller bioactive peptides, such as a-melanocytestimulating hormone (a-MSH) and b-endorphin (Mains & Eipper 2000). Secretion of POMC-derived peptides in both cell types is stimulated by both the hypothalamic peptides, arginine vasopressin and corticotropin-releasing factor (CRF; Vale et al 1981, Lundblad & Roberts 1988.…”

Section: Introductionmentioning

confidence: 99%

Strain-specific steroidal control of pituitary function

Lee¹,

Peng²,

Desjardins³

et al. 2007

Journal of Endocrinology

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We have previously shown that 7B2 null mice on the 129/SvEvTac (129) genetic background die at 5 weeks of age with hypercorticosteronemia due to a Cushing's-like disease unless they are rescued by adrenalectomy; however, 7B2 nulls on the C57BL/6NTac (B6) background remain healthy, with normal steroid levels. Since background exerts such a profound influence on the phenotype of this mutation, we have evaluated whether these two different mouse strains respond differently to high circulating steroids by chronically treating wild-type 129 and B6 mice with the synthetic steroid dexamethasone (Dex). Dex treatment decreased the dopamine content of the neurointermediate lobes (NIL) of 129 mice, leading to NIL enlargement and increased total D 2 R mRNA in the 129, but not the B6, NIL. Despite the decrease in this inhibitory transmitter, Dex-treated 129 mice exhibited reduced circulating a-melanocyte-stimulating hormone (a-MSH) along with reduced POMC-derived peptides compared with controls, possibly due to reduced POMC content in the NIL. In contrast, Dex-treated B6 mice showed lowered cellular ACTH, unchanged a-MSH and b-endorphin, and increased circulating a-MSH, most likely due to increased cleavage of NIL ACTH by increased PC2. Dextreated 129 mice exhibited hyperinsulinemia and lowered blood glucose, whereas Dex-treated B6 mice showed slightly increased glucose levels despite their considerably increased insulin levels. Taken together, our results suggest that the endocrinological response of 129 mice to chronic Dex treatment is very different from that of B6 mice. These straindependent differences in steroid sensitivity must be taken into account when comparing different lines of transgenic or knockout mice.

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Proopiomelanocortin Synthesis and Cell‐Specific Processing

Cited by 4 publications

References 202 publications

Endocannabinoid system and proopiomelanocortin gene expression in peripartal bovine liver in response to prepartal plane of nutrition

Endocannabinoid system and proopiomelanocortin gene expression in peripartal bovine liver in response to prepartal plane of nutrition

Cleavage of recombinant proenkephalin and blockade mutants by prohormone convertases 1 and 2: an in vitro specificity study

Strain-specific steroidal control of pituitary function

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