Regulation of gamma-glutamyl transpeptidase activity by Ca(2+)- and protein kinase C-dependent pathways in Sertoli cells.
gamma-Glutamyl transpeptidase (gamma-GTP) activity in Sertoli cells can be stimulated by FSH. This cAMP-dependent metabolic event can be enhanced when Sertoli cells are co-cultured with germ cells, suggesting that different signal transduction pathways may be involved in the regulation of gamma-GTP activity. In this study we examined the participation of Ca(2+)- and protein kinase C (pkC)-dependent signal transduction pathways in the regulation of basal and FSH-stimulated gamma-GTP activity. Under basal conditions, the increase in extracellular Ca2+ concentration or the addition of the Ca2+ ionophore 4Br-A23187 produced a decrease in gamma-GTP activity. Conversely, blockage of voltage-dependent Ca2+ channels with verapamil or nifedipine or inhibition of Ca(2+)-calmodulin dependent processes with trifluoperazine resulted in an increase in gamma-GTP activity. To study the role of a pkC-dependent pathway the effects of low doses of staurosporine were evaluated. Under these experimental conditions an increase in gamma-GTP activity was observed. It was then investigated whether these signal transduction pathways could interact with the FSH-stimulated cAMP-dependent pathway to regulate gamma-GTP activity. Increase in extracellular Ca2+ concentration, the addition of 4Br-A23187 or the blockage of voltage-dependent Ca2+ channels did not modify FSH-stimulated gamma-GTP activity. However, staurosporine produced an additional increase in FSH-stimulated gamma-GTP activity and this effect was also observed when cells were stimulated with dbcAMP. In summary, our data are consistent with an inhibitory role of Ca(2+)-calmodulin- and pkC-dependent pathways in the regulation of basal gamma-GTP activity. Similar to what has been shown for other Sertoli cell parameters, a pkC-dependent pathway can interact with the FSH-stimulated cAMP-dependent pathway. The precise steps involved in this interaction are still unknown.
Meroni
S
S
Centro de Investigaciones Endocrinológicas (CEDIE), Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Cánepa
D
D
Pellizzari
E
E
Schteingart
H
H
Cigorraga
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000201:enzymology*; D012756:Sheep; D015398:Signal Transduction; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D005640:Follicle Stimulating Hormone; D005723:gamma-Glutamyltransferase; D011493:Protein Kinase C; D002118:Calcium