Nitric oxide is produced in the brain by the neuronal Nitric Oxide Synthase (nNOS) and carries out a wide range of functions by acting as neurotransmitter-like molecule. Gonadal hormones are involved in the regulation of the brain nitrergic system. We previously demonstrated that estradiol, via classical estrogen receptors (ERs), regulates NOS activity in the supraoptic (SON) and paraventricular nucleus (PVN) of the hypothalamus, acting through both ERα and ERβ. Magnocellular and parvocellular neurons in the SON and in the PVN express also the G protein-coupled ER (GPER). In this study we have assessed whether GPER is also involved in the regulation of NADPH-diaphorase in the SON and the PVN. Adult female ovariectomized rats were treated with G1, a selective GPER agonist, or with G1 in combination with G15, a selective GPER antagonist. G1 treatment decreased NADPH-diaphorase expression in the SON and in all PVN subnuclei. The treatment with G1+G15 effectively rescued the G1-dependent decrease of NADPH-d expression in both brain regions. In addition, the activation of ERK 1/2, one of the kinases involved in the GPER–dependent intracellular signaling pathway and in NOS phosphorylation, was assessed in the same brain nuclei. Treatment with G1 significantly decreases the number of pERK 1/2 positive cells in the SON and PVN, while the treatment with G1+G15 significantly recovered its number to control values. These findings suggest that the activation of GPER in the SON and the PVN inhibits the phosphorylation of ERK 1/2, which induces a decrease in NADPH-diaphorase expression.

NADPH-Diaphorase colocalizes with GPER and is modulated by the GPER agonist G1 in the supraoptic and paraventricular nuclei of ovariectomized female rats

GRASSI, Daniela;PANZICA, Giancarlo;
2017

Abstract

Nitric oxide is produced in the brain by the neuronal Nitric Oxide Synthase (nNOS) and carries out a wide range of functions by acting as neurotransmitter-like molecule. Gonadal hormones are involved in the regulation of the brain nitrergic system. We previously demonstrated that estradiol, via classical estrogen receptors (ERs), regulates NOS activity in the supraoptic (SON) and paraventricular nucleus (PVN) of the hypothalamus, acting through both ERα and ERβ. Magnocellular and parvocellular neurons in the SON and in the PVN express also the G protein-coupled ER (GPER). In this study we have assessed whether GPER is also involved in the regulation of NADPH-diaphorase in the SON and the PVN. Adult female ovariectomized rats were treated with G1, a selective GPER agonist, or with G1 in combination with G15, a selective GPER antagonist. G1 treatment decreased NADPH-diaphorase expression in the SON and in all PVN subnuclei. The treatment with G1+G15 effectively rescued the G1-dependent decrease of NADPH-d expression in both brain regions. In addition, the activation of ERK 1/2, one of the kinases involved in the GPER–dependent intracellular signaling pathway and in NOS phosphorylation, was assessed in the same brain nuclei. Treatment with G1 significantly decreases the number of pERK 1/2 positive cells in the SON and PVN, while the treatment with G1+G15 significantly recovered its number to control values. These findings suggest that the activation of GPER in the SON and the PVN inhibits the phosphorylation of ERK 1/2, which induces a decrease in NADPH-diaphorase expression.
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www.karger.com/journals/nen/nen_jh.htm
Estrogen; Extracellular signal-regulated kinase; G protein-coupled estrogen receptors; Hypothalamus; NADPH-diaphorase; Nitric oxide synthase; Paraventricular nucleus; Supraoptic nucleus; Endocrinology, Diabetes and Metabolism; Endocrinology; Endocrine and Autonomic Systems; Cellular and Molecular Neuroscience
Grassi, Daniela; Lagunas, Natalia; Pinos, Helena; Panzica, Giancarlo; Garcia-Segura, Luis Miguel; Collado, Paloma
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1630434
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