Inhibition of protein kinase C by staurosporine increases estrogen secretion by rat Sertoli cells.
We have examined the effect of inhibition of protein kinase C activity by staurosporine on estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Staurosporine lead to a dose-related increase in estradiol secretion independent of FSH, such that with 100 nmol/l staurosporine basal estradiol levels increased 10-fold. The maximal response seen with staurosporine alone (100 nmol/l) or in combination with FSH (0.4-8 IU/l) was similar to that seen with a saturating dose of FSH (8 IU/l). There was no evidence of synergy between FSH and staurosporine. Activation of protein kinase C by phorbol 12,13 dibutyrate (10(-7) mol/l) resulted in a 53-74% inhibition of estradiol production provoked by FSH (8 IU/l), staurosporine (5-100 nmol/l) or staurosporine in combination with FSH. Staurosporine (5-100 nmol/l), in the absence or presence of FSH, was unable to overcome inhibition of estradiol secretion by phorbol ester, indicating the presence of at least two independent binding sites on protein kinase C for these molecules. Forskolin (1 mumol/l)- and dibutyryl cAMP (1 mmol/l)-stimulated estradiol secretion was inhibited by 31 +/- 5% and 64 +/- 5% respectively, by phorbol 12,13 dibutyrate (10(-7) mol/l). We conclude that FSH-induced estradiol secretion in immature rat Sertoli cells is affected by protein kinase C activity.
Lambert
A
A
Department of Medicine (Clinical Biochemistry), University of Manchester, Hope Hospital, Salford, UK.
Talbot
J A
JA
Mitchell
R
R
Robertson
W R
WR
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004336:Drug Antagonism; D004958:Estradiol / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000378:metabolism*; D019311:Staurosporine
D000470:Alkaloids; D015240:Phorbol 12,13-Dibutyrate; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D011493:Protein Kinase C; D019311:Staurosporine