Tamoxifen, protein kinase C and rat sperm mitochondria.
Tamoxifen at a dose of 400 microg/kg/day has been reported to reduce the fertility of adult male rats and alter the pattern of cauda sperm motility from forward progressive to circular yawing type. Since sperm motility is powered by mitochondria, the effect of tamoxifen on mitochondrial function was studied. Tamoxifen treatment significantly increased rhodamine 123 fluorescent dye uptake by sperm mitochondria, reflecting an altered mitochondrial membrane potential. ATP and DAG levels, activities of glycolytic enzymes, creatine kinase and PKC all remained unaffected by tamoxifen. This is also the first report describing the presence of PKC alpha and beta in rat sperm. Morphological and biochemical integrity of sperm membranes was determined by electron microscopy and malondialdehyde levels, which were unaltered after tamoxifen treatment. This study indicates that the altered sperm motility induced by tamoxifen is accompanied by changes in mitochondrial membrane potential, but in the absence of any detectable change in membrane integrity, lipid peroxidation, ATP levels and activities of glycolytic enzymes, creatine kinase and PKC.
Saberwal
Gurveen Sethi
GS
Department of Neuroendocrinology, National Institute for Research in Reproductive Health, Parel, 400 012 Mumbai, India. g-saberwal@northwestern.edu
Gill-Sharma
Manjit K
MK
Balasinor
Nafisa
N
Choudhary
Jyoti
J
Padwal
Varsha
V
Juneja
H S
HS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003402:Creatine Kinase / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006019:Glycolysis; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D020112:Rhodamine 123 / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D013629:Tamoxifen / Q000494:pharmacology*
D005456:Fluorescent Dyes; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020112:Rhodamine 123; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D003402:Creatine Kinase