title: Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.
abstract: Neurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex. Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.0 nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50% after 90 min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90 min and by 3.5 times after 3 h, respectively. GnRH action is mediated by LH and 1.0 nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90 min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72 h. These data indicate for the first time that GnRH regulates both cholesterol and steroid biosynthesis in human neuronal-like cells and suggest a new physiological role for GnRH in the brain.
authors.affiliation: Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Viale G. Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rosati
authors.forename: Niccolò
authors.initials: N
authors.lastname: Sturli
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Cungi
authors.forename: Matteo
authors.initials: M
authors.lastname: Morello
authors.forename: Fabio
authors.initials: F
authors.lastname: Villanelli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bartolucci
authors.forename: Claudia
authors.initials: C
authors.lastname: Finocchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Danza
mesh_terms: D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D037101:Luteinizing Hormone, beta Subunit; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human