Unsaturated fatty acids disrupt Smad signaling in gonadotrope cells leading to inhibition of FSHβ gene expression.

Unsaturated fatty acids disrupt Smad signaling in gonadotrope cells leading to inhibition of FSHβ gene expression. Endocrinology. 2013 Nov 18; Authors: Garrel G, Simon V, Denoyelle C, Ishaq M, Rouch C, Dairou J, Magnan C, Migrenne S, Cruciani-Guglielmacci C, Cohen-Tannoudji J Abstract Reproductive function is highly dependent on nutritional input. We recently provided evidence that the unsaturated ω6 fatty acid, linoleic acid (linoleic), interferes with transcription and secretion of the gonadotropin LH, highlighting the existence of a lipid sensing in pituitary gonadotropes. Here, we show using a combination of in vivo and in vitro models, that linoleic differentially regulates Lhb and Fshb expression. Central exposure of rats to linoleic over 7 days was associated with increase of Lhb but not Fshb transcript levels. Consistently, exposure of rat pituitary cells or LβT2 cells to linoleic increased Lhb while it dramatically decreased Fshb transcript levels without affecting its stability. This effect was also induced by ω9 and ω3 polyunsaturated fatty acid but not by saturated palmitic acid. Analysis of the underlying mechanisms in LβT2 cells using siRNA revealed that Egr-1 mediates linoleic stimulation of Lhb expression. Furthermore, we demonstrated that linoleic counteract activin and BMP2 stimulation of Fshb expression. Using Western blot and Smad-responsive reporter gene assays, linoleic was shown to decrease basal Smad2/3 phosphoryl...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research