Testing the antagonistic effect of follistatin on BMP family members in ovine granulosa cells.
Follistatin was first demonstrated as an activin-binding protein, neutralizing its actions. However, there is emerging evidence that follistatin inhibits the action of other members of the transforming growth factor beta(TGFbeta) / bone morphogenetic protein (BMP) superfamily. Recently, numerous BMP factors have been shown to play important roles in regulating folliculogenesis and ovulation rate in mammals, and such a potential antagonistic role of follistatin is of particular interest in the context of ovarian function. Using a biological test based on progesterone production by ovine primary granulosa cells in culture, we show that follistatin was a strong antagonist of activin A, but not BMP-2 or BMP-4 actions. In contrast, noggin, a known specific BMP antagonist, had no effect on activin A but strongly neutralized BMP-2 and BMP-4 actions. BMP-6 action was only slightly reduced by both follistatin and noggin. Our data led to the conclusion that follistatin would not represent a determinant physiological modulator of the biological effect of BMP factors on granulosa cells.
Pierre
Alice
A
INRA, Physiologie de la Reproduction et des Comportements, UMR 6175 INRA-CNRS-Université de Tours-Haras Nationaux, Nouzilly, France.
Pisselet
Claudine
C
Monget
Philippe
P
Monniaux
Danielle
D
Fabre
Stéphane
S
D028341:Activins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D038681:Follistatin / Q000494:pharmacology*; D006107:Granulosa Cells; D028322:Inhibin-beta Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012756:Sheep; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099176:Noggin Protein
D028341:Activins; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D038681:Follistatin; D028322:Inhibin-beta Subunits; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C422405:activin A