Inhibitory action of in vitro ethanol and acetaldehyde exposure on LHRH-and phorbol ester-stimulated testosterone secretion by rat testicular interstitial cells.
Ethanol and acetaldehyde have been shown to inhibit testicular steroidogenesis. However the mechanism(s) of signal transduction involved in their action is still unclear. We examined the possible involvement of phospholipid-sensitive, calcium-dependent protein kinase (protein Kinase C, PK-C) in the intracellular mechanism of action of ethanol and acetaldehyde by stimulating testosterone production in rat testicular interstitial cells with LHRH and the phorbol ester PDBu, both of which activate PK-C at receptor (LHRH) and post-receptor (PDBu) sites. Ethanol (2000 mg %) inhibited 10(-7) M LHRH and 200 nM PDBu-stimulated testosterone production by 81 +/- 4.7% and 60 +/- 20.4%, respectively. Acetaldehyde (20 mg %) reduced the amount of testosterone produced by 10(-7) M LHRH and 200 nM PDBu by 59.4 +/- 1.2% and 52.5 +/- 5.4% respectively. Basal testosterone levels were unaffected by ethanol and reduced by acetaldehyde. However, the functional test of cell viability by preincubating cells with these doses of ethanol and acetaldehyde did not decrease their ability to respond appropriately to subsequent stimulation with LHRH, demonstrating that cell viability was unaffected by incubation with these drugs. The data presented here suggest that direct ethanol and acetaldehyde exposure results in a reduced ability of the testicular interstitial cells to respond to stimulation of PK-C pathway.
Wanderley
M I
MI
Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
Udrisar
D P
DP
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000378:metabolism*
D010703:Phorbol Esters; D007987:Gonadotropin-Releasing Hormone; D000431:Ethanol; D013739:Testosterone; D000079:Acetaldehyde