Estrogen modulation of hypothalamic neurons: Activation of multiple signaling pathways and gene expression changes

Malyala, Anna; Kelly, Martin J.; Rønnekleiv, Oline K.

doi:10.1016/j.steroids.2005.03.004

Cited by 116 publications

(70 citation statements)

References 121 publications

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“…28 Gabarapl1 is also highly expressed in gonadotropin-releasing hormone (GnRH) neurons, 29,30 a neuronal population that is regulated by estrogen. Indeed, estrogen receptors are highly expressed in the hypothalamus 21,29 and play a major role in the regulation of the reproductive axis through their control on the release of luteinizing hormone and follicle-stimulating hormone at the anterior pituitary.…”

Section: The Gabarap Familymentioning

confidence: 99%

“…Indeed, estrogen receptors are highly expressed in the hypothalamus 21,29 and play a major role in the regulation of the reproductive axis through their control on the release of luteinizing hormone and follicle-stimulating hormone at the anterior pituitary. Moreover, the primary neurotransmitter inputs to these neurons are GABA A and glutamate, which exert their effects in the neurons through GABA A receptors GABARAPL1 (Structural Genomic Consortium, code: 2R2Q) are also highly similar.…”

Section: The Gabarap Familymentioning

confidence: 99%

See 1 more Smart Citation

GABARAPL1 (GEC1): Original or copycat?

Grand

Chakrama²,

Seguin-Py³

et al. 2011

Autophagy

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Section: The Gabarap Familymentioning

confidence: 99%

Section: The Gabarap Familymentioning

confidence: 99%

GABARAPL1 (GEC1): Original or copycat?

Grand

Chakrama²,

Seguin-Py³

et al. 2011

Autophagy

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“…Studies are forthcoming on the cross-talk between rapid membrane-initiated and long-term nuclear-initiated steroid actions (Lagrange et al, 1994, Lagrange et al, 1997, Wagner et al, 2001b, Vasudevan et al, 2001, Kow and Pfaff, 2004, Malyala et al, 2005, Qiu et al, 2006b, Qiu et al, 2006a, Roepke et al, 2007. For example, it has been found that both acute effects of E2 and the transcriptional changes alter excitability of hypothalamic neurons , Malyala et al, 2005, Qiu et al, 2006a.…”

Section: β-Estradiol and Gnrh Neurosecretionmentioning

confidence: 99%

“…For example, it has been found that both acute effects of E2 and the transcriptional changes alter excitability of hypothalamic neurons , Malyala et al, 2005, Qiu et al, 2006a. In addition, the estrogen-induced membrane actions in the ventromedial nucleus (VMH) of the hypothalamus can potentiate its genomic effects on lordosis behavior (Kow and Pfaff, 2004).…”

Section: β-Estradiol and Gnrh Neurosecretionmentioning

confidence: 99%

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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“…Estrogens are known to rapidly modulate neuronal activity in the cortex and hippocampus. In the cortex, estrogen potentiates excitatory synapses via increased sensitivity to glutamate through multiple mechanisms which include altered cellular responsiveness to inotropic glutamate receptor activation, opioid, dopamine, and GABA receptors (reviewed here (Kelly and Ronnekleiv, 2009;Malyala et al, 2005;Sellers et al, 2015)) as well as more long term effects by regulation of the brain transcriptome (Duclot and Kabbaj, 2015). Studied extensively in the hippocampus, estradiol increases sensitivity to glutamate or related receptors in both males and females, albeit by differing mechanisms (Oberlander and Woolley, 2016).…”

Section: Discussionmentioning

confidence: 99%

Sex and regional differences in microglia morphology and complement receptor 3 are independent of constitutive neuroinflammatory protein concentrations in healthy mice

Young

Rothers

Castaneda

et al. 2018

Preprint

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Microglia are highly ramified brain phagocytes that are finely tuned to surrounding neuronal and glial activity. Combined, microglia morphology, dynamic process movement, phagocytic, and neuroinflammatory responses aid in the detection of changed neuronal function, maintenance, and restoration of neural networks during physiology and pathophysiologic conditions. An awareness of how microglia diversity in the healthy brain relates to brain region and sex differences would inform brain physiology, further delineate risk factors of central nervous system (CNS) diseases, and clarify mechanisms of dichotomous injury outcomes between men and women. Microglia morphology, complement receptor 3 (CR3), and neuroinflammatory proteins were studied in the somatosensory cortex and hippocampus CA1 among male and female (estrus, diestrus and ovarian failure) mice (C67Bl/6J, 16 weeks) to discover relationships among microglia morphology, region, sex, and neuroinflammatory environment. The human post-menopause period was modeled in mice using 4-vinylcyclohexene diepoxide injections which induced accelerated ovarian failure. Using methods to quantify ramification, shape, and complexity, we discovered differences in microglia morphologies according to brain region and sex group. Microglia endpoints, process length, and complexity were increased in the female ovarian failure group when compared to other sex groups. Microglia were smaller and less complex in the hippocampus region versus the cortex. Microglia phagocytic receptor CR3 was assessed using immunohistochemistry methods and was increased in the female diestrus cortex when compared to male and females in estrus; no sex differences were observed in the hippocampus. Neuroinflammatory protein concentrations were screened using Multiplex Luminex methods and were detected in cortex homogenates, however, no differences among the sex groups were observed. Microglia morphology and CR3 are diverse in the adult healthy Understanding sex and region specific differences in the brain's surveillance and maintenance system will provide insight into the variability of patient risk and outcomes in CNS diseases.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.26937v1 | CC BY 4.0 Open Access |

show abstract

Estrogen modulation of hypothalamic neurons: Activation of multiple signaling pathways and gene expression changes

Cited by 116 publications

References 121 publications

GABARAPL1 (GEC1): Original or copycat?

GABARAPL1 (GEC1): Original or copycat?

Membrane-initiated estrogen signaling in hypothalamic neurons

Sex and regional differences in microglia morphology and complement receptor 3 are independent of constitutive neuroinflammatory protein concentrations in healthy mice

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