title: Long-chain unsaturated fatty acids reduce the transcriptional activity of the rat follicle-stimulating hormone β-subunit gene.
abstract: Here, we assessed the effects of long-chain fatty acids (LCFAs) and the LCFA receptor agonist GW9508 on the transcription of the gonadotropin subunit genes Cga, Lhb and Fshb because LCFA receptor GPR120 was observed in mouse gonadotropes in our recent study. A transcription assay using LβT2 cells demonstrated that LCFAs, oleic acid, α-linolenic acid, docosahexaenoic acid and palmitate, repressed the expression of Cga, Lhb, and Fshb at concentrations between 50 and 100 µM. On the other hand, treatment with 10 µM unsaturated LCFAs, oleic acid, α-linolenic acid and docosahexaenoic acid, repressed only Fshb expression, while the same dose of a saturated LCFA, palmitate, had no effect on the expression of gonadotropin subunit genes. Furthermore, GW9508 did not affect promoter activity. Next, we examined deletion mutants of the upstream region of Fshb and found that the upstream regulatory region (-2824 to -2343 bp) of Fshb was responsible for the notable repression by 10 µM unsaturated LCFAs. Our results suggest that the upstream region of Fshb is susceptible to unsaturated LCFAs. In addition, unsaturated LCFAs play a role in repressing Fshb expression through the distal -2824 to -2343 bp region, which might be independent of the LCFA receptor GPR120 pathway.
authors: Laboratory of Environmental Physiology, Department of Life Science, School of Science and Engineering, Kinki University, Osaka 577-8502, Japan.
authors: Ryutaro
authors: R
authors: Moriyama
authors: Tsubasa
authors: T
authors: Yamazaki
authors: Takako
authors: T
authors: Kato
authors: Yukio
authors: Y
authors: Kato
mesh_terms: D000818:Animals; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D017930:Genes, Reporter; D008744:Methylamines / Q000737:chemistry; D009154:Mutation; D019301:Oleic Acid / Q000378:metabolism; D010168:Palmitates / Q000737:chemistry; D011422:Propionates / Q000737:chemistry; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D017962:alpha-Linolenic Acid / Q000737:chemistry
chemical_list: D005231:Fatty Acids, Unsaturated; C533284:Ffar4 protein, rat; D037201:Follicle Stimulating Hormone, beta Subunit; C515630:GW9508; D008744:Methylamines; D010168:Palmitates; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D019301:Oleic Acid