TY - JOUR
T1 - Involvement of lipids in dimethoate-induced inhibition of testosterone biosynthesis in rat interstitial cells
AU - Astiz, Mariana
AU - Hurtado De Catalfo, Graciela E.
AU - De Alaniz, María J.T.
AU - Marra, Carlos Alberto
N1 - Funding Information:
Acknowledgments This study was supported by a grant from Consejo Nacional de Investigaciones Científicas y Técnicas (CONI-CET), Argentina. We would like to thank Mrs. Agustina Zardis de Cobeñas, Eva Illara de Bozzolo, and Norma Cristalli for their excellent technical assistance.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/8
Y1 - 2009/8
N2 - The mechanism involved in the inhibition of testosterone (Te) biosynthesis after a sub-chronic exposure to low doses of dimethoate (D) was studied in rat interstitial cells (IC). Expression of COX-2 in IC isolated from D-treated rats increased by 44% over C data, while transcription of StAR decreased by approx. 50% and the expression of this protein was diminished by approximately 40%. PGE2 and PGF2α were increased by 61 and 78%, respectively. Te concentration decreased by 49% in IC homogenates. Concomitantly, plasma concentration of LH and FSH both increased. Araquidonate (ARA) and C22 fatty acyl chains in phospholipids from IC mitochondrial fraction decreased by approx. 30% after D treatment. Protein carbonyls, lipoperoxides and nitrite content increased while α-tocopherol and the antioxidant capacity of the soluble cellular fraction decreased significantly. Stimulation with h-CG 10 nM overnight failed to overcome the inhibition caused by D on both Te biosynthesis and 3β- and 17β-hydroxysteroid dehydrogenases. Decreased Te biosynthesis may be attributed to (1) inhibition of StAR protein activity due to the stimulation of COX-2 and the overproduction of PGF2α, (2) decreased stimulatory effect of ARA on StAR with a subsequent reduction in the availability of CHO for the androgenic pathway, and/or (3) indirect inhibition of steroidogenic enzymes by a lower transcriptional rate caused by elevated PGF2α. Rofecoxib administration prevents the deleterious effect(s) exerted by D.
AB - The mechanism involved in the inhibition of testosterone (Te) biosynthesis after a sub-chronic exposure to low doses of dimethoate (D) was studied in rat interstitial cells (IC). Expression of COX-2 in IC isolated from D-treated rats increased by 44% over C data, while transcription of StAR decreased by approx. 50% and the expression of this protein was diminished by approximately 40%. PGE2 and PGF2α were increased by 61 and 78%, respectively. Te concentration decreased by 49% in IC homogenates. Concomitantly, plasma concentration of LH and FSH both increased. Araquidonate (ARA) and C22 fatty acyl chains in phospholipids from IC mitochondrial fraction decreased by approx. 30% after D treatment. Protein carbonyls, lipoperoxides and nitrite content increased while α-tocopherol and the antioxidant capacity of the soluble cellular fraction decreased significantly. Stimulation with h-CG 10 nM overnight failed to overcome the inhibition caused by D on both Te biosynthesis and 3β- and 17β-hydroxysteroid dehydrogenases. Decreased Te biosynthesis may be attributed to (1) inhibition of StAR protein activity due to the stimulation of COX-2 and the overproduction of PGF2α, (2) decreased stimulatory effect of ARA on StAR with a subsequent reduction in the availability of CHO for the androgenic pathway, and/or (3) indirect inhibition of steroidogenic enzymes by a lower transcriptional rate caused by elevated PGF2α. Rofecoxib administration prevents the deleterious effect(s) exerted by D.
UR - http://www.scopus.com/inward/record.url?scp=68349092771&partnerID=8YFLogxK
U2 - 10.1007/s11745-009-3323-5
DO - 10.1007/s11745-009-3323-5
M3 - Journal articles
C2 - 19579042
AN - SCOPUS:68349092771
SN - 0024-4201
VL - 44
SP - 703
EP - 718
JO - Lipids
JF - Lipids
IS - 8
ER -
