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The opiorphin gene (ProL1) and its homologues function in erectile physiology
Author(s) -
Tong Yuehong,
Tar Moses,
Melman Arnold,
Davies Kelvin
Publication year - 2008
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2008.07631.x
Subject(s) - erectile dysfunction , erectile function , medicine , cell physiology , endocrinology , erectile tissue , andrology , cell , biology , genetics
OBJECTIVE To determine if ProL1 , a member of the opiorphin family of genes, can modulate erectile physiology, as it encodes a peptide which acts as a neutral endopeptidase inhibitor, other examples of which ( Vcsa1 , hSMR3A ) modulate erectile physiology. MATERIALS AND METHODS We cloned members of the opiorphin family of genes into the same mammalian expression backbone (pVAX); 100 µg of these plasmids (pVAX‐Vcsa1, ‐hSMR3A, ‐hSMR3B and ‐ProL1) were injected intracorporally into retired breeder rats and the affect on erectile physiology assessed visually, by histology and by measuring the intracavernous pressure (ICP) and blood pressure (BP). As a positive control, rats were treated with pVAX‐hSlo (expressing the MaxiK potassium channel) and as a negative control the empty backbone plasmid was injected (pVAX). We also compared the level of expression of ProL1 in corporal tissue of patients not reporting erectile dysfunction (ED), ED associated with diabetes and ED not caused by diabetes. RESULTS Gene transfer of plasmids expressing all members of the opiorphin family had a similar and significant effect on erectile physiology. At the concentration used in these experiments (100 µg) they resulted in higher resting ICP, and histological and visual analysis showed evidence of a priapic‐like condition. After electrostimulation of the cavernous nerve, rats had significantly better ICP/BP than the negative control (pVAX). Gene transfer of pVAX‐hSlo increased the ICP/BP ratio to a similar extent to the opiorphin homologues, but with no evidence for a priapic‐like condition. Corpora cavernosa tissue samples obtained from men with ED, regardless of underlying causes, had significant down‐regulation of both hSMR3A and ProL1 . CONCLUSION All members of the human opiorphin family of genes can potentially modulate erectile physiology. Both hSMR3 and ProL1 are down‐regulated in the corpora of men with ED, and therefore both genes can potentially act as markers of ED.