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Decreased Immunoreactivity of the Polypeptide Precursor Pro‐Opiomelanocortin ( POMC ) and the Prohormone Convertase PC 1/3 After Chronic Ethanol Exposure in S prague‐ D awley Rats
Author(s) -
Navarro Montserrat,
Cubero Inmaculada,
Thiele Todd E.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01951.x
Subject(s) - prohormone , medicine , endocrinology , chemistry , hypothalamus , prohormone convertase , proopiomelanocortin , melanocortin , neuropeptide , peptide hormone , biology , biochemistry , hormone , receptor
Background The melanocortin ( MC ) peptides and opioid peptide β‐endorphin are cleaved from the polypeptide precursor pro‐opiomelanocortin ( POMC ). POMC ‐derived peptides are generated by extensive posttranslational processing that involves several enzymes including prohormone convertase 1/3 and 2 ( PC 1/3 and PC 2). Because ethanol ( E t OH ) decreases POMC m RNA levels, we determined whether the exposure to an E t OH ‐containing diet ( ED ) would significantly reduce central immunoreactivity ( IR ) of POMC , PC 1/3, PC 2, and β‐endorphin. Methods Male S prague‐ D awley rats were given 18 days of access to a normal rodent chow or a control diet ( CD ), or short‐term (4 days) or long‐term (18 days) access to an ED . At the end of the study, rats were perfused with 4% paraformaldehyde, and their brains were sectioned into sets for processing with POMC , PC 1/3, PC 2, and β‐endorphin IR . Results Rats exposed to an ED for 18 days ( ED 18) exhibited significant reductions of POMC and PC 1/3 IR in the arcuate nucleus of the hypothalamus ( A rc) relative to rats pair‐fed a CD . On the other hand, rats exposed to an ED did not show any changes of central β‐endorphin or PC 2 IR relative to rats pair‐fed a CD , regardless of length of exposure. Because there were no differences in body weights or caloric intake between the CD and ED groups, reductions of POMC and PC 1/3 IR in ED ‐treated rats are best explained by E t OH exposure rather than altered energy balance. Conclusions This study shows that E t OH site‐specifically reduces POMC and PC 1/3 IR in rat brain. These observations are consistent with E t OH ‐induced reductions of α‐melanocyte‐stimulating hormone (α‐ MSH ) and POMC IR that were previously reported. As MC agonists have been shown to blunt EtOH intake in rodents, exogenous MC receptor agonists, as well as targets that may increase the synthesis of endogenous α‐ MSH (e.g., PC 1/3), may have therapeutic value for treating alcohol abuse disorders and alcoholism.