Conjugated linoleic acids attenuate FSH- and IGF1-stimulated cell proliferation; IGF1, GATA4, and aromatase expression; and estradiol-17β production in buffalo granulosa cells involving PPARγ, PTEN, and PI3K/Akt.
Conjugated linoleic acid (CLA) has drawn much interest in last two decades in the area ranging from anticancer activity to obesity. A number of research papers have been published recently with regard to CLA's additional biological functions as reproductive benefits. However, not much is known how this mixture of isomeric compounds mediates its beneficial effects particularly on fertility. In this study, we demonstrated the cross talk between downstream signaling of CLA and important hormone regulators of endocrine system, i.e. FSH and IGF1, on buffalo granulosa cell function (proliferation and steroidogenesis). Experiments were performed in primary serum-free buffalo granulosa cell culture, where cells were incubated with CLA in combination with FSH (25 ng/ml) and IGF1 (50  ng/ml). Results showed that 10 μM CLA inhibits FSH- and IGF1-induced granulosa cell proliferation; aromatase, GATA4, and IGF1 mRNA; and estradiol-17β production. Western blot analysis of total cell lysates revealed that CLA intervenes the IGF1 signaling by decreasing p-Akt. In addition, CLA was found to upregulate peroxisome proliferator-activated receptor-gamma (PPARG) and phosphatase and tensin homolog (PTEN) level in granulosa cells. Further study using PPARG- and PTEN-specific inhibitors supports the potential role of CLA in granulosa cell proliferation and steroidogenesis involving PPARG, PTEN, and PI3K/Akt pathway.
Animal Biochemistry Division, Molecular Endocrinology Laboratory, National Dairy Research Institute, Karnal 132001, Haryana, India.
Isha
I
Sharma
Dheer
D
Singh
D000818:Animals; D001141:Aromatase / Q000235:genetics; D002020:Buffaloes / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D050991:GATA4 Transcription Factor / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D047495:PPAR gamma / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology
D050991:GATA4 Transcription Factor; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D012333:RNA, Messenger; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase