Progesterone triggers rapid transmembrane calcium influx and/or calcium mobilization from endoplasmic reticulum, via a pertussis-insensitive G-protein in granulosa cells in relation to luteinization process.
We investigated the early effects (5-60 s) of progesterone (1 pM-0.1 microM) on cytosolic free calcium concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (InsP3) formation in nonluteinized and in vitro luteinized porcine granulosa cells (pGCs). Progesterone increased [Ca2+]i and InsP3 formation within 5 s in both cell types. Progesterone induced calcium mobilization from the endoplasmic reticulum via the activation of a phospholipase C linked to a pertussis-insensitive G-protein. This process was controlled by protein kinases C and A. In contrast, only nonluteinized pGCs showed a Ca2+ influx via dihydropyridine-insensitive calcium channel. In both cell types, the nuclear progesterone receptor antagonist RU-38486 did not inhibit the progesterone-induced increase in [Ca2+]i, progesterone immobilized on bovine serum albumin, which did not enter the cell, increased [Ca2+]i within 5 s and was a full agonist, but less potent than the free progesterone; pertussis toxin did not inhibit progesterone effect on InsP3. In conclusion, progesterone may interact with membrane unconventional receptors that belong to the class of membrane receptors coupled to a phospholipase C via a pertussis toxin-insensitive G-protein. The source of the Ca2+ for the progesterone-induced increase in [Ca2+]i also depends on the stage of cell luteinization.
Machelon
V
V
Institut National de la Santé et de la Recherche Médicale U 355, Institut Fédératif des Cytokines de Paris Sud, Clamart, France.
Nomé
F
F
Grosse
B
B
Lieberherr
M
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D006107:Granulosa Cells / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008184:Luteal Cells / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D037342:Pertussis Toxin; D011374:Progesterone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D010566:Virulence Factors, Bordetella; C075151:progesterone 3-(O-carboxymethyl)oxime-bovine serum albumin; D012710:Serum Albumin, Bovine; D015735:Mifepristone; D011374:Progesterone; D004533:Egtazic Acid; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium