Public health policy in recent years has favoured a reduction in saturated fats in favour of polyunsaturated fats due to the numerous health benefits of polyunsaturated fatty acids (PUFAs). Previous studies have demonstrated that PUFAs modulate gonadal steroidogenesis. We have therefore investigated the hypothesis that PUFAs modify steroidogenesis through affecting components of the cholesterol metabolising machinery, including steroidogenic acute regulatory (StAR) protein and the nuclear receptors peroxisome proliferator activated receptor (PPAR) and liver X receptor (LXR). Both PPARs and LXR can act as sensors of lipids derived from either the diet or intracellular metabolism, and can regulate diverse aspects of cholesterol and fatty acid homeostasis.
In vivo studies were carried out using 2 groups of synchronized Welsh mountain ewes (n=8) that were individually feed either a control, or Linseed (n-3 PUFA) diet for 6 weeks. At the end of the experiment all animals were humanely slaughtered and adrenal glands and ovaries were collected for analysis of protein expression by western blotting. The Y1 mouse adrenocortical cell line was used to investigate the effects of PUFAs in vitro.
Both PPARγ2 and LXR were highly expressed in the ovine adrenals and ovaries but their levels of expression were unaffected by the high n-3 PUFA diet. However, levels of StAR protein expression were significantly inhibited in both ovaries (control 1.433±0.32, n-3 0.384±0.09 optical density units, n=8, P<0.05) and adrenals (control 4.760±0.846, n−3 1.975±0.557 optical density units, n=8, P<0.05). In Y1 cells, low levels of PPAR and LXR were detected under control conditions. In accord with the in vivo findings, PUFA treatment in vitro significantly inhibited StAR protein expression. We conclude that PUFAs in vivo and in vitro significantly decrease expression of StAR protein and thereby compromise steroidogenesis. The mechanistic nature of the inhibitory action of PUFAs does not appear to include either PPARγ2 or LXR.
Supported by the Wellcome Trust and BBSRC