title: Unsaturated fatty acids stimulate LH secretion via novel PKCepsilon and -theta in gonadotrope cells and inhibit GnRH-induced LH release.
abstract: The activity of pituitary gonadotrope cells, crucial for reproductive function, is regulated by numerous factors including signals related to nutritional status. In this work, we demonstrated, for the first time, that in vivo central exposure of rats to lipids intracarotid infusion of a heparinized triglyceride emulsion selectively increases the expression of pituitary LH subunit genes without any alteration of pituitary GnRH receptor and hypothalamic GnRH or Kiss-1 transcript levels. Furthermore, we showed that unsaturated fatty acids (UFA), oleate and linoleate, increase LH release in a dose-dependent manner as well as LHβ mRNA levels in both immortalized LβT2 gonadotrope cell line and rat primary cell cultures. In contrast, the saturated palmitate was ineffective. ACTH or TSH secretion was unaffected by UFA treatment. We demonstrated in LβT2 cells that linoleate effect is mediated neither by activation of membrane fatty acid (FA) receptors GPR40 or GPR120 although we characterized these receptors in LβT2 cells, nor through nuclear peroxisome proliferator-activated receptors. Furthermore, linoleate β-oxidation is not required for its action on LH secretion. In contrast, pharmacological inhibition of protein kinase C (PKC) or ERK pathways significantly prevented linoleate-stimulated LH release. Accordingly, linoleate was shown to activate novel PKC isoforms, PKCε and -θ, as well as ERK1/2 in LβT2 cells. Lastly, unsaturated, but not saturated, FA inhibited GnRH-induced LH secretion in LβT2 cells as well as in pituitary cell cultures. Altogether, these results suggest that the pituitary is a relevant site of FA action and that UFA may influence reproduction by directly interfering with basal and GnRH-dependent gonadotrope activity.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, Equipe d'accueil conventionnée, Centre National de la Recherche Scientifique 4413, 75205 Paris Cedex 13, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Garrel
authors.forename: Violaine
authors.initials: V
authors.lastname: Simon
authors.forename: Chantal
authors.initials: C
authors.lastname: Denoyelle
authors.forename: Céline
authors.initials: C
authors.lastname: Cruciani-Guglielmacci
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Migrenne
authors.forename: Raymond
authors.initials: R
authors.lastname: Counis
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
authors.forename: Joëlle
authors.initials: J
authors.lastname: Cohen-Tannoudji
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D052681:Gonadotrophs / Q000187:drug effects* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007527:Isoenzymes / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000502:physiology*; D051744:Protein Kinase C-epsilon / Q000502:physiology*; D000074121:Protein Kinase C-theta; D051381:Rats
chemical_list: D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; C497257:Prkce protein, rat; C489591:Prkcq protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta