Apoptosis of bovine granulosa cells: Intracellular pathways and differentiation.
Follicular atresia in granulosa and theca cells occurs by apoptosis through weak hormonal stimulation. We have previously proposed an in vitro model to study this process by inducing apoptosis in BGC-1, a bovine granulosa cell line, and in primary cultures from ovaries with or without corpus luteum (CPGB+ and CPGB-, respectively), with different doses of gonadotropin releasing hormone (GnRH) analogs (leuprolide acetate (LA) as agonist and antide as antagonist). BGC-1 represent immature granulosa cells, whereas CPGB represent different degrees of luteinization. Our aim was to evaluate the intracellular pathways involved in the GnRH regulation of apoptosis in BGC-1. Treatment with LA 100nM but not with antide led to an increase in BAX over BCL-2 expression, showing antagonism of antide. All treatments inhibited phospholipase-D (PLD) activity compared to control, implying agonist behavior of antide. Progesterone in vitro production and 3β-hydroxysteroid dehydrogenase (3β-HSD) expression revealed different degrees of luteinization: BGC-1 were immature, whereas CPGB+ were less differentiated than CPGB-. We concluded that LA-induced apoptosis in BGC-1 occurs by activation of the mitochondrial pathway and by inhibition of PLD activity and that antide might work both as an antagonist of the intrinsic pathway and as an agonist of the extrinsic protection pathway by inhibiting PLD activity.
['Carou|M C|MC|', 'Cruzans|P R|PR|', 'Maruri|A|A|', 'Farina|M G|MG|', 'Fiorito|C D|CD|', 'Olea|G|G|', 'Lombardo|D M|DM|']
D000818:Animals D017209:Apoptosis D002417:Cattle D002454:Cell Differentiation D002460:Cell Line D002478:Cells, Cultured D004789:Enzyme Activation D005260:Female D018507:Gene Expression Regulation, Developmental D019254:Genes, bcl-2 D007987:Gonadotropin-Releasing Hormone D006107:Granulosa Cells D016729:Leuprolide D008928:Mitochondria D009842:Oligopeptides D010053:Ovary D010739:Phospholipase D D015398:Signal Transduction D051028:bcl-2-Associated X Protein
Apoptosis Bovine granulosa cells Differentiation BGC-1 3β-HSD GnRH analogs