Role of proteoglycans on testosterone synthesis by purified Leydig cells from immature and mature rats.
In order to characterize an involvement of proteoglycans (PG) in the regulation of Leydig cell function, we have examined the effects of para-nitrophenyl-beta-D-xyloside (PNPX), a specific inhibitor of PG synthesis and para-nitrophenyl-beta-D-galactoside (PNPG), an inefficient structural analogue, on testosterone production by purified Leydig cells from immature and mature rats, in the presence or not of various concentrations of hCG during 24 h. Whatever the age, the addition of PNPX induces a decrease of [35S] and [3H] incorporations into cell layer associated-PG; these latter being less numerous (-50 and -25%, respectively in immature and mature rat), and less sulfated (-40%) when compared to control Leydig cells. In immature Leydig cells, the inhibition of PG synthesis decreases both the basal and weakly stimulable-hCG or -(Bu)2cAMP or -LH testosterone synthesis. In mature Leydig cells, the PG inhibition has no effect on testosterone production both in the absence of hCG and in the presence of weak amounts of hCG but increases it in the presence of subsaturating hCG concentrations. Whatever the age, the inhibition of PG synthesis is ineffective in the presence of saturating amounts of either hCG or (Bu)2cAMP. These effects are maintained in the presence of MIX, PMA, but are not observed in the presence of 22R-hydroxycholesterol. Therefore, our results suggest that in rat Leydig cells, the inhibition of PG synthesis affects the signal transduction at a step distal to cyclic AMP and more precisely, the cholesterol supply to the mitochondria by acting on its cellular distribution (free and esterified cholesterol).
Grudet
N
N
Laboratoire de Biochimie-IRBA, Université de Caen, France.
Bonnamy
P J
PJ
Le Goff
D
D
Carreau
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006027:Glycosides / Q000494:pharmacology*; D006888:Hydroxycholesterols / Q000494:pharmacology; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D009598:Nitrophenylgalactosides / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D015398:Signal Transduction; D013431:Sulfates / Q000378:metabolism; D013737:Testis / Q000254:growth & development; D013739:Testosterone / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D006025:Glycosaminoglycans; D006027:Glycosides; D006888:Hydroxycholesterols; D011509:Proteoglycans; D013431:Sulfates; C003585:22-hydroxycholesterol; C008646:4-nitrophenyl beta-D-xyloside; D009598:Nitrophenylgalactosides; C059200:4-nitrophenylgalactoside; D013739:Testosterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D005944:Glucosamine; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine