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Submitted on September 21, 2004
Accepted on November 9, 2004
Dept. Pharmaco-Biology (Faculty of Pharmacy), Dept. of Cell Biology, Centro Sanitario; University of Calabria 87030 Arcavacata di Rende (CS) ITALY
* To whom correspondence should be addressed. E-mail: aquisav{at}libero.it.
A striking feature of insulin expression is its almost complete restriction to
-cells of the pancreatic islet in normal mammals. Here we show that insulin is expressed in and secreted from human ejaculated spermatozoa. Both insulin transcript and protein were detected. In addition, the large differences in insulin secretion, assessed by RIA, between uncapacitated and capacitated sperm suggest a role for insulin in capacitation. Insulin had an oscillatory secretory pattern involving glucose dose-dependent increases and significant decreases during the blockage of an insulin autocrine effect. It appears that the effect of glucose on the fertilizing ability of sperm is mediated by glucose metabolism through the pentose phosphate pathway (PPP). Then, we evaluated the autocrine effect of sperm-insulin on glucose metabolism by studying G6PDH activity, the key rate-limiting enzyme in the PPP. The simultaneous decrease in both insulin release and G6PDH activity induced by blocking the autocrine insulin effect with three different procedures (blockage of insulin release by nifedipine; immune neutralization of the released insulin by anti-insulin serum; blockage of an insulin intracellular effector like PI3K by wortmannin), strongly suggests a physiological role of sperm-insulin on these two events. Insulin secretion by spermatozoa may provide an autocrine regulation of glucose metabolism based on their energetic needs independent of systemic insulin. In conclusion, these data open a new area of study in male reproduction.
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