Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice

Sica, M.; Martini, Mariangela; Viglietti‐Panzica, C.; Panzica, Giancarlo

doi:10.1186/1471-2202-10-78

Cited by 41 publications

(41 citation statements)

References 75 publications

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“…Intriguingly, in contrast with previous studies suggesting that estrogen could modulate hypothalamic nNOS gene expression [58,81,82,83,84], these changes in NO secretion seen during the estrous cycle are not associated with changes in nNOS protein synthesis but rather with changes in nNOS activity [62,85]. Estradiol induces the formation of a NMDA-R-nNOS complex in neurons of the preoptic region [62,85], thus enhancing NO secretion [86] by coupling nNOS to its main stimulatory calcium influx pathway [12,14] (box).…”

Section: Neuronal Nitric Oxide Modulates Gnrh Neuronal Activity and Scontrasting

confidence: 43%

Nitric Oxide as Key Mediator of Neuron-to-Neuron and Endothelia-to-Glia Communication Involved in the Neuroendocrine Control of Reproduction

Bellefontaine

Hanchate²,

Parkash³

et al. 2011

Neuroendocrinology

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Nitric oxide (NO) is a peculiar chemical transmitter that freely diffuses through aqueous and lipid environments and plays a role in major aspects of brain function. Within the hypothalamus, NO exerts critical effects upon the gonadotropin-releasing hormone (GnRH) network to maintain fertility. Here, we review recent evidence that NO regulates major aspects of the GnRH neuron physiology. Far more active than once thought, NO powerfully controls GnRH neuronal activity, GnRH release and structural plasticity at the neurohemal junction. In the preoptic region, neuronal nitric oxide synthase (nNOS) activity is tightly regulated by estrogens and is found to be maximal at the proestrus stage. Natural fluctuations of estrogens control both the differential coupling of this Ca²⁺-activated enzyme to glutamate N-methyl-D-aspartic acid receptor channels and phosphorylation-mediated nNOS activation. Furthermore, NO endogenously produced by neurons expressing nNOS acutely and directly suppresses spontaneous firing in GnRH neurons, which suggests that neuronal NO may serve as a synchronizing switch within the preoptic region. At the median eminence, NO is spontaneously released from an endothelial source and follows a pulsatile and cyclic pattern of secretion. Importantly, GnRH release appears to be causally related to endothelial NO release. NO is also highly involved in mediating the dialogue set in motion between vascular endothelial cells and tanycytes that control the direct access of GnRH neurons to the pituitary portal blood during the estrous cycle. Altogether, these data raise the intriguing possibility that the neuroendocrine brain uses NO to coordinate both GnRH neuronal activity and GnRH release at key stages of reproductive physiology.

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Section: Neuronal Nitric Oxide Modulates Gnrh Neuronal Activity and Scontrasting

confidence: 43%

Nitric Oxide as Key Mediator of Neuron-to-Neuron and Endothelia-to-Glia Communication Involved in the Neuroendocrine Control of Reproduction

Bellefontaine

Hanchate²,

Parkash³

et al. 2011

Neuroendocrinology

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“…Increased numbers of nNitric oxide synthase immunoreactive neurons were found in the ARC during proestrus and in the POA during estrus. As these regions show large numbers of ERa, this study supports the conclusion of Pfaff and coworkers that E2 modulates expression of nNitric oxide synthase, which stimulates estrous behavior via activation of the nitric oxide signaling pathway (Sica et al, 2009). …”

Section: Genomic Regulation Of Estrous Behavior: Central Mechanisms Isupporting

confidence: 89%

“…Together, the products of these genes play a role in the induction of the behavioral expression of estrus. A recent study of Sica et al (2009) in female mice showed changes in nNitric oxide synthase expression in the hypothalamus during the estrous cycle. Increased numbers of nNitric oxide synthase immunoreactive neurons were found in the ARC during proestrus and in the POA during estrus.…”

Section: Genomic Regulation Of Estrous Behavior: Central Mechanisms Imentioning

confidence: 98%

Estrous behavior in dairy cows: identification of underlying mechanisms and gene functions

Bôer

Veerkamp

Beerda

et al. 2010

Animal

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Selection in dairy cattle for a higher milk yield has coincided with declined fertility. One of the factors is reduced expression of estrous behavior. Changes in systems that regulate the estrous behavior could be manifested by altered gene expression. This literature review describes the current knowledge on mechanisms and genes involved in the regulation of estrous behavior. The endocrinological regulation of the estrous cycle in dairy cows is well described. Estradiol (E2) is assumed to be the key regulator that synchronizes endocrine and behavioral events. Other pivotal hormones are, for example, progesterone, gonadotropin releasing hormone and insulin-like growth factor-1. Interactions between the latter and E2 may play a role in the unfavorable effects of milk yield-related metabolic stress on fertility in high milk-producing dairy cows. However, a clear understanding of how endocrine mechanisms are tied to estrous behavior in cows is only starting to emerge. Recent studies on gene expression and signaling pathways in rodents and other animals contribute to our understanding of genes and mechanisms involved in estrous behavior. Studies in rodents, for example, show that estrogen-induced gene expression in specific brain areas such as the hypothalamus play an important role. Through these estrogen-induced gene expressions, E2 alters the functioning of neuronal networks that underlie estrous behavior, by affecting dendritic connections between cells, receptor populations and neurotransmitter releases. To improve the understanding of complex biological networks, like estrus regulation, and to deal with the increasing amount of genomic information that becomes available, mathematical models can be helpful. Systems biology combines physiological and genomic data with mathematical modeling. Possible applications of systems biology approaches in the field of female fertility and estrous behavior are discussed.

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“…There are many reports indicating that estrogen regulates nNOS expression in both up-and down-regulated manner. [37][38][39] Combined with the above discussion, sex hormone, especially estrogen, has a considerable impact on CA formation and can greatly influence CA formation. This is because there may be a different result in CA formation of eNOS-deficient mice with different sex.…”

Section: Discussionmentioning

confidence: 99%

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

Aoki

Nakagawa

Kataoka

et al. 2011

Laboratory Investigation

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The rupture of cerebral aneurysm (CA) and subsequent subarachnoid hemorrhage can cause fatal results. Recent experimental findings have suggested that the mechanism of CA formation is based on chronic inflammation in arterial walls by hemodynamic force. Endothelial nitric oxide synthase (eNOS) protects arterial walls from vascular inflammation by relieving hemodynamic force through nitric oxide (NO) production. Thus, the expression and protective role of eNOS in CA formation have been investigated in this study. In this study, experimental induced rodent CA models by carotid ligation and systemic hypertension were used. The expression of eNOS was examined in rat CA models and revealed that it was decreased at the site of CA formation. Next, CA was induced in eNOS À/À mice to clarify the role of eNOS in CA formation. In eNOS À/À mice, the incidence of CA formation was similar to that found in wild-type mice. In CA walls of eNOS À/À mice, the expression of neuronal nitric oxide synthase (nNOS) was upregulated compared with that in wild-type mice, suggesting the compensatory effect of nNOS. Hence, eNOS À/À nNOS À/À mice were generated, underwent CA induction and confirmed that eNOS À/À nNOS À/À mice exhibited an increased incidence of CA formation accompanied by accelerated macrophage infiltration. These results suggested that the deficiency of eNOS could be compensated by nNOS upregulation in cerebral arteries and that the eNOS and nNOS complementarily had the protective role in CA formation. The results of this study will provide us with new insight about the mechanisms of CA formation and the functional redundancy between eNOS and nNOS in cerebral arteries.

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Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice

Cited by 41 publications

References 75 publications

Nitric Oxide as Key Mediator of Neuron-to-Neuron and Endothelia-to-Glia Communication Involved in the Neuroendocrine Control of Reproduction

Nitric Oxide as Key Mediator of Neuron-to-Neuron and Endothelia-to-Glia Communication Involved in the Neuroendocrine Control of Reproduction

Estrous behavior in dairy cows: identification of underlying mechanisms and gene functions

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

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