title: Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland.
abstract: Although the fetal pineal gland does not secrete melatonin, the fetus is exposed to melatonin of maternal origin. In the non-human primate fetus, melatonin acts as a trophic hormone for the adrenal gland, stimulating growth while restraining cortisol production. This latter physiological activity led us to hypothesize that melatonin may influence some fetal functions critical for neonatal adaptation to extrauterine life. To test this hypothesis we explored (i) the presence of G-protein-coupled melatonin binding sites and (ii) the direct modulatory effects of melatonin on noradrenaline (norepinephrine)-induced middle cerebral artery (MCA) contraction, brown adipose tissue (BAT) lypolysis and ACTH-induced adrenal cortisol production in fetal sheep. We found that melatonin directly inhibits the response to noradrenaline in the MCA and BAT, and also inhibits the response to ACTH in the adrenal gland. Melatonin inhibition was reversed by the melatonin antagonist luzindole only in the fetal adrenal. MCA, BAT and adrenal tissue displayed specific high-affinity melatonin binding sites coupled to G-protein (K(d) values: MCA 64 +/- 1 pm, BAT 98.44 +/- 2.12 pm and adrenal 4.123 +/- 3.22 pm). Melatonin binding was displaced by luzindole only in the adrenal gland, supporting the idea that action in the MCA and BAT is mediated by different melatonin receptors. These direct inhibitory responses to melatonin support a role for melatonin in fetal physiology, which we propose prevents major contraction of cerebral vessels, restrains cortisol release and restricts BAT lypolysis during fetal life.
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Torres-Farfan
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Valenzuela
authors.forename: Mauricio
authors.initials: M
authors.lastname: Mondaca
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Valenzuela
authors.forename: Bernardo
authors.initials: B
authors.lastname: Krause
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.forename: Raquel
authors.initials: R
authors.lastname: Riquelme
authors.forename: Anibal J
authors.initials: AJ
authors.lastname: Llanos
authors.forename: Maria
authors.initials: M
authors.lastname: Seron-Ferre
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000502:physiology*; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D008550:Melatonin