Diacylglycerol rather than Ca2+ mediates GnRH inhibition of FSH induced steroidogenesis in ovarian granulosa cells.
Treatment of cultured granulosa cells with PLC or GnRH stimulated the rapid generation of DAG and phosphoinositide turnover. The PKC activators PLC (3 mU/ml) and TPA (10(-7)M) or the decapeptide GnRH (10(-6)M) elicited similar inhibitory responses on FSH or cAMP stimulated granulosa cell steroidogenesis. Mobilization of intracellular Ca2+ with A23187 (10(-8)M) was followed by a slight increase in the steroidogenic activity of cultured granulosa cells, whereas elevation of extracellular K+ (50 mM) largely augmented the steroid biosynthetic activity of the granulosa cells. These results suggest that the inhibitory effect of GnRH on granulosa cell steroidogenesis is mediated by generation of DAG, rather than by increases in intracellular Ca2+ concentrations.
Fanjul
L F
LF
Departamento de Endocrinología Celular y Molecular, Facultad de Medicina, Universidad de Las Palmas de Gran Canaria, Spain.
Déniz
A
A
Quintana
J
J
Santana
P
P
Gonzalez
J
J
Estevez
F
F
Ruiz de Galarreta
C M
CM
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism*; D004343:Drug Implants; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011375:Progesterone Reductase / Q000378:metabolism*; D051381:Rats; D012826:Silicone Elastomers; D013229:Stearic Acids / Q000378:metabolism; D013251:Steroid Isomerases / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D004075:Diglycerides; D004343:Drug Implants; D009097:Multienzyme Complexes; D010716:Phosphatidylinositols; D012826:Silicone Elastomers; D013229:Stearic Acids; D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D000001:Calcimycin; C031183:stearic acid; D003994:Bucladesine; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D011375:Progesterone Reductase; D010738:Type C Phospholipases; D013251:Steroid Isomerases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium