Effects of unsaturated fatty acids on progesterone secretion and selected protein kinases in goat granulosa cells

Domest Anim Endocrinol. 2010 May;38(4):272-83. doi: 10.1016/j.domaniend.2009.12.002. Epub 2010 Jan 13.

Abstract

Previous studies in cattle have shown influences of dietary unsaturated fatty acid (UFA) supplementation on ovarian function. However, it is unclear whether these UFA exert direct or indirect effects on ovarian steroid production or their mechanisms of action. We have recently shown that 5'AMP-activated protein kinase (AMPK) regulates progesterone secretion through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK ERK1/2) in rodent granulosa cells. Here, we investigated the effects of 3 UFAs, oleic acid (OA), linoleic acid (LA), and alpha-linolenic acid (ALA) on progesterone secretion in goat granulosa cells. Finally, we examined the effects of UFAs on MAPK ERK1/2 and AMPK phosphorylation in these granulosa cells. Oleic acid and LA (10 microM each), but not ALA (100 microM), increased progesterone secretion (P<0.05) in the presence or absence of insulin-like growth factor (IGF)-1 (10(-8) M) or FSH (5 x 10(-8)M). The different AMPK subunits, except for gamma3, are present in the goat ovary. Treatment with metformin (10mM), an activator of AMPK, increased AMPK phosphorylation (P<0.05) and reduced progesterone secretion by 50% (P<0.05) in the basal state and in response to IGF-1 or FSH in goat granulosa cells. Oleic acid and LA had no effect on AMPK phosphorylation, whereas they rapidly increased MAPK ERK1/2 phosphorylation (P<0.05). Finally, U0126, a MAPK ERK1/2 inhibitor, decreased OA- and LA-induced progesterone secretion (P<0.05), suggesting that these UFAs could stimulate progesterone secretion partly through MAPK ERK1/2 in the absence of IGF-1 and FSH in goat granulosa cells. The involvement of AMPK in this process remains to be demonstrated. Taken together, some fatty acids could improve ovarian steroidogenesis through the MAPK ERK1/2 signaling pathway and, consequently, have beneficial effects on goat fertility.

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Fatty Acids, Unsaturated / pharmacology*
  • Female
  • Follicle Stimulating Hormone / pharmacology
  • Goats / metabolism*
  • Granulosa Cells / drug effects*
  • Granulosa Cells / enzymology
  • Granulosa Cells / metabolism
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Linoleic Acid / pharmacology
  • Metformin / pharmacology
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Oleic Acid / pharmacology
  • Ovary / enzymology
  • Phosphorylation / drug effects
  • Progesterone / metabolism*
  • Protein Kinases / metabolism*
  • alpha-Linolenic Acid / pharmacology

Substances

  • Fatty Acids, Unsaturated
  • alpha-Linolenic Acid
  • Oleic Acid
  • Progesterone
  • Insulin-Like Growth Factor I
  • Follicle Stimulating Hormone
  • Metformin
  • Linoleic Acid
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Adenylate Kinase