17β-Estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP

Minami, Taketsugu; Osuga, Yutaka; Nabekura, Junichi; Fukuda, Atsuo

doi:10.1016/0006-8993(90)90092-p

Cited by 131 publications

(79 citation statements)

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“…Using intracellular recording techniques, it was found that fast perfusion of estrogen (100 pM) hyperpolarized arcuate neurons within seconds in a hypothalamic slice preparation and that this effect was reversed within minutes of washing out estrogen (Kelly et al, 1980). Similar actions of E2 were also demonstrated in hypothalamic ventromedial nucleus (VMH) and amygdala neurons, even in the presence of protein synthesis inhibitors (Nabekura et al, 1986, Minami et al, 1990. Later, it was found that GnRH neurons, identified post hoc using a combination of intracellular dye labeling and immunocytochemical staining, were a target of estrogen actions (Kelly et al, 1984).…”

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confidence: 86%

Membrane-initiated estrogen signaling in hypothalamic neurons

Kelly

Rønnekleiv

2008

Molecular and Cellular Endocrinology

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SummaryIt is well known that many of the actions of 17β-estradiol (E2) in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there is compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. But it is not well understood how estrogen signals via membrane receptors, and how these signals impact not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for sometime that E2 can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, E2 can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review will consider our current knowledge of rapid membrane-initiated and intracellular signaling by E2 in the hypothalamus, the nature of receptors involved and how they contribute to homeostatic functions. KeywordsERα; ERβ; GPCR (G protein-coupled receptor); mER (membrane estrogen receptor that is a GPCR) Electrophysiological studies in the 1960's and 1970's suggested that gonadal steroids could directly modulate the electrical activity of hypothalamic neurons

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confidence: 86%

Membrane-initiated estrogen signaling in hypothalamic neurons

Kelly

Rønnekleiv

2008

Molecular and Cellular Endocrinology

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“…1), including the modulation of intracellular calcium [44,55,122,165,175,209] and protein kinase C (PKC; [266,276]). There is also evidence that membrane effects of estrogens can activate intracellular signaling pathways involving cyclic AMP (cAMP; [103,170,254]), protein kinase A (PKA; [104,141,266]), the "mitogen activated protein kinases" (or MAP kinases; [39,122,153,205,260,269,276]), and the tyrosine kinases [39]. The activation of these intracellular signaling pathways results primarily in phosphorylations/dephosphorylations producing different kinds of physiological responses such as the decoupling of a receptor from its effector system [141,[171][172][173] or the modulation of the catalytic activity of an enzyme [191].…”

Section: Non-genomic Effects On Cell Functionmentioning

confidence: 99%

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

2006

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Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

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confidence: 99%

“…However, there is growing recognition of the importance of rapid mechanisms of estrogen signaling within a diverse array of cell types (Falkenstein et al, 2000;Kelly and Levin, 2001). In particular, it is of note that many of the brain regions displaying sexually dimorphic responses to estrogen also exhibit rapid estrogen effects (Yagi, 1973;Minami et al, 1990;Lagrange et al, 1995;Gu et al, 1999;Rudick and Woolley, 2003) and the possibility that nongenomic mechanisms may also contribute to sexually differentiated responses to estrogen has been suggested (Simerly, 2002) but not documented. To define brain regions responding to estrogen in a rapid, non-genomic manner, we and others have used the phosphorylation of CREB by estrogen as a marker of rapid changes in intracellular signaling (Gu et al, 1996;Zhou et al, 1996;Abraham et al, 2003;Abraham et al, 2004).…”

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confidence: 99%

Major sex differences in non-genomic estrogen actions on intracellular signaling in mouse brain in vivo

Ábrahám

Herbison

2005

Neuroscience

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Abstract-Rapid effects of estrogen have now been identified throughout the brain but the extent to which these actions may be different in males and females is unknown. Previous work has shown that estrogen rapidly phosphorylates Ser 133 of cAMP responsive element binding protein (CREB) through a non-genomic mechanism. Using this indicator, we have examined here whether non-genomic estrogen actions occur in a sexually dimorphic manner within the adult brain. Male and female mice were gonadectomized and 3 weeks later treated with 17-␤-estradiol or vehicle for 1 h prior to perfusion fixation and subsequent CREB and phosphorylated CREB (pCREB) immunostaining of brain sections. The numbers of cells expressing CREB immunoreactivity were not altered by estrogen treatment or different in males and females in any of the brain regions examined. However, estrogen treatment significantly (P<0.05) increased pCREB-immunoreactive cell numbers in the medial preoptic area, ventrolateral division of the ventromedial nucleus, medial septum and CA1 region of the hippocampus of female mice. In contrast, estrogen increased pCREB levels in the medial septum and CA1 but not in the preoptic area or ventromedial nucleus of male mice. To evaluate the extent to which non-genomic estrogen actions may be sexually differentiated within a single neuronal phenotype, dual labeling immunocytochemistry was undertaken to evaluate the gonadotropin-releasing hormone ( A variety of neuronal circuits in the mammalian brain exhibit robust sex differences in structure and function (De Vries, 1990;Simerly, 2002). Hypothalamic regions such as the medial preoptic area (mPOA) and ventromedial nucleus (VMN) contain key sexually differentiated neuronal circuits responsible for controlling reproductive function (Pfaff et al., 1994;Flanagan-Cato, 2000;Simerly, 2002). For example, the GnRH neurons within the mPOA represent the final output neurons of the network involved in regulating gonadal function (Levine, 2003). Whereas estrogen stimulates a massive increment in GnRH secretion to induce ovulation in the female mammal, it has no similar effect in males (Herbison, 1998). In addition, clear sex differences have been observed in the effects of estrogen on networks involved in regulating male and female sexual behavior (Pfaff et al., 1994;Flanagan-Cato, 2000). Interestingly, these sexually differentiated actions of estrogen are not confined solely to circuits involved in the modulation of reproductive function but also exist within brain regions such as the hippocampus (Woolley, 2000;Leranth et al., 2003).The mechanisms underlying the sexually dimorphic effects of estrogen on brain function in the adult are unclear. As one possibility, estrogen may regulate different numbers or populations of cells within a specific brain region of males and females. This is likely to be the case for the sexually dimorphic nucleus of the preoptic area and the spinal nucleus of the bulbocavernosus in the rat (for review see Simerly, 2002) where major sex differences in neuronal n...

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17β-Estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP

Cited by 131 publications

References 32 publications

Membrane-initiated estrogen signaling in hypothalamic neurons

Membrane-initiated estrogen signaling in hypothalamic neurons

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

Major sex differences in non-genomic estrogen actions on intracellular signaling in mouse brain in vivo

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