Erythropoietin and testicular steroidogenesis: the role of second messengers.
It has been demonstrated that erythropoietin (EPO) influences rat and human Leydig cell steroidogenesis, stimulating testosterone production through a direct and specific receptor-mediated mechanism. The aim of this study was to investigate the mechanism by which recombinant human erythropoietin (rHuEPO) exerts its stimulatory effect on rat Leydig cells. Recombinant human EPO did not induce, at any dose tested (10(-10) to 10(-13) mol/l), an increase in either cAMP or cGMP, suggesting that in Leydig cells the effect of rHuEPO does not involve the adenylate or guanylate-cyclase systems. The role of transmembrane calcium flux in rHuEPO-stimulated steroidogenesis was studied by evaluating the effect of calcium channel blocker, verapamil, and by the 45Ca2+ uptake method. Verapamil did not influence rHuEPO-induced testosterone secretion and rHuEPO did not modify calcium recycling, indicating that calcium transmembrane flux is not involved in the rHuEPO effect. The protein kinase C inhibitor staurosporine (10, 30, 100 and 300 nmol/l) inhibited rHuEPO-stimulated testicular steroidogenesis in a dose-dependent manner. This indirect evidence suggests that the stimulatory effect of rHuEPO on rat Leydig cells may involve protein kinase C activation.
Institute of Internal Medicine, University of Padova, Italy.
C
C
Foresta
R
R
Mioni
P
P
Bordon
F
F
Gottardello
A
A
Nogara
M
M
Rossato
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D015290:Second Messenger Systems; D019311:Staurosporine; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D011994:Recombinant Proteins; D004921:Erythropoietin; D013739:Testosterone; D014700:Verapamil; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D019311:Staurosporine; D002118:Calcium