title: Morphine treatment selectively regulates expression of rat pituitary POMC and the prohormone convertases PC1/3 and PC2.
abstract: The prohormone convertases, PC1/3 and PC2 are thought to be responsible for the activation of many prohormones through processing including the endogenous opioid peptides. We propose that maintenance of hormonal homeostasis can be achieved, in part, via alterations in levels of these enzymes that control the ratio of active hormone to prohormone. In order to test the hypothesis that exogenous opioids regulate the endogenous opioid system and the enzymes responsible for their biosynthesis, we studied the effect of short-term morphine or naltrexone treatment on pituitary PC1/3 and PC2 as well as on the level of pro-opiomelanocortin (POMC), the precursor gene for the biosynthesis of the endogenous opioid peptide, β-endorphin. Using ribonuclease protection assays, we observed that morphine down-regulated and naltrexone up-regulated rat pituitary PC1/3 and PC2 mRNA. Immunofluorescence and Western blot analysis confirmed that the protein levels changed in parallel with the changes in mRNA levels and were accompanied by changes in the levels of phosphorylated cyclic-AMP response element binding protein. We propose that the alterations of the prohormone processing system may be a compensatory mechanism in response to an exogenous opioid ligand whereby the organism tries to restore its homeostatic hormonal milieu following exposure to the opioid, possibly by regulating the levels of multiple endogenous opioid peptides and other neuropeptides in concert.
authors.affiliation: Department of Radiation Medicine, Loma Linda University, Loma Linda, CA 92350, USA.|Division of Endocrinology, Department of Medicine, Cedars-Sinai Research Institute-UCLA School of Medicine, Los Angeles, CA 90048, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Science-UCLA School of Medicine, Los Angeles, CA 90059, USA.
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
authors.affiliation: Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Science-UCLA School of Medicine, Los Angeles, CA 90059, USA.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Science-UCLA School of Medicine, Los Angeles, CA 90059, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Anghel
authors.affiliation: Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Science-UCLA School of Medicine, Los Angeles, CA 90059, USA.
authors.forename: Enma V
authors.initials: EV
authors.lastname: Paez Espinosa
authors.affiliation: Division of Endocrinology, Department of Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island 02903, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Stuart
authors.affiliation: Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Science-UCLA School of Medicine, Los Angeles, CA 90059, USA.|College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Kabirullah
authors.initials: K
authors.lastname: Lutfy
authors.affiliation: Division of Endocrinology, Department of Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island 02903, USA.|Department of Molecular Biology, Cell Biology & Biochemistry, Brown University, Providence, Rhode Island 02903, USA.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Nillni
authors.affiliation: Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Science-UCLA School of Medicine, Los Angeles, CA 90059, USA.|Division of Endocrinology, Department of Medicine, Cedars-Sinai Research Institute-UCLA School of Medicine, Los Angeles, CA 90048, USA.
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Friedman
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009292:Narcotic Antagonists; D009294:Narcotics; D012333:RNA, Messenger; D009271:Naltrexone; D011333:Pro-Opiomelanocortin; D009020:Morphine; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2
keywords: Drug addiction; Endorphin; Opioids; Pituitary; Post-translational processing; Prohormone convertase
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