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 1.0nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50\% after 90min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90min and by 3.5 times after 3h, respectively. GnRH action is mediated by LH and 1.0nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72h. 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.

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells / F. Rosati;N. Sturli;M. C. Cungi;M. Morello;F. Villanelli;G. Bartolucci;C. Finocchi;A. Peri;M. Serio;G. Danza. - In: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY. - ISSN 0960-0760. - STAMPA. - 124:(2011), pp. 77-83. [10.1016/j.jsbmb.2011.01.012]

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.

ROSATI, FABIANA;STURLI, NICCOLO';MORELLO, MATTEO;BARTOLUCCI, GIAN LUCA;PERI, ALESSANDRO;SERIO, MARIO;DANZA, GIOVANNA
2011

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 1.0nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50\% after 90min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90min and by 3.5 times after 3h, respectively. GnRH action is mediated by LH and 1.0nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72h. 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.
2011
124
77
83
F. Rosati;N. Sturli;M. C. Cungi;M. Morello;F. Villanelli;G. Bartolucci;C. Finocchi;A. Peri;M. Serio;G. Danza
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/433461
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