G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus

Llorente, Ricardo; Marraudino, Marilena; Carrillo, Beatriz; Bonaldo, Brigitta; Simon-Areces, Julia; Abellanas-Pérez, Pedro; Rivero-Aguilar, Marina; Fernández-García, José Manuel; Pinos, Helena; García‐Segura, Luis M.; Collado, Paloma; Grassi, Daniela

doi:10.3389/fendo.2020.00537

Cited by 17 publications

(5 citation statements)

References 91 publications

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“…When injected into the amygdaloid complex it produces anxiolytic actions (Frye & Walf, 2004). Within the medial amygdala, expression of membrane‐associated G protein‐coupled oestrogen receptor 1 (GPER) displays remarkable oestrus cycle‐linked plasticity (Llorente et al, 2020). A similar plasticity of expression of GPER has also been reported in the PAG (Spary et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Panic‐like responses of female Wistar rats confronted by Bothrops alternatus pit vipers, or exposure to acute hypoxia: Effect of oestrous cycle

Sgobbi

Figueiredo

Frias

et al. 2021

Eur J of Neuroscience

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Anxiety‐related diseases are more than twice as common in women than in men, and in women, symptoms may be exacerbated during the late luteal phase of the menstrual cycle. Despite this, most research into the underlying mechanisms, which drives drug development, have been carried out using male animals. In an effort to redress this imbalance, we compared responses of male and female Wistar rats during exposure to two unconditioned threatening stimuli that evoke panic‐related defensive behaviours: confrontation with a predator (Bothrops alternatus) and acute exposure to hypoxia (7% O2). Threatened by venomous snake, male and female rats initially displayed defensive attention, risk assessment, and cautious interaction with the snake, progressing to defensive immobility to overt escape. Both males and females displayed higher levels of risk assessment but less interaction with the predator. They also spent more time in the burrow, displaying inhibitory avoidance, and more time engaged in defensive attention, and non‐oriented escape behaviour. In females, anxiety‐like behaviour was most pronounced in the oestrous and proestrus phases whereas panic‐like behaviour was more pronounced during the dioestrus phase, particularly during late dioestrus. Acute hypoxia evoked panic‐like behaviour (undirected jumping) in both sexes, but in females, responsiveness in late dioestrus was significantly greater than at other stages of the cycle. The results reveal that females respond in a qualitatively similar manner to males during exposure to naturally occurring threatening stimuli, but the responses of females is oestrous cycle dependent with a significant exacerbation of panic‐like behaviour in the late dioestrus phase.

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Section: Discussionmentioning

confidence: 99%

Panic‐like responses of female Wistar rats confronted by Bothrops alternatus pit vipers, or exposure to acute hypoxia: Effect of oestrous cycle

Sgobbi

Figueiredo

Frias

et al. 2021

Eur J of Neuroscience

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“…128 Studies have revealed that GPER is also expressed in the BNST, amygdala and hippocampus. 129,130 Testosterone's effects on the AVP and OT systems may be mediated directly via its biding at the AR or by ERs after its conversion into 17β-estradiol by the enzyme aromatase (Figure 3). Both AR and ER mechanisms may be at play, as supported by the fact that AVP gene expression in the PVN increases after treatment with 17βestradiol and testosterone in ovariectomized rats.…”

Section: S E X Hormone Modul Ation Of Social Recog Nitionmentioning

confidence: 99%

“…GPER has been found in both the PVN and the SON of male and female rats, where it co‐localizes with both OT and AVP neurons 128 . Studies have revealed that GPER is also expressed in the BNST, amygdala and hippocampus 129,130 …”

Section: Sex Hormone Modulation Of Social Recognitionmentioning

confidence: 99%

Neuroendocrine underpinning of social recognition in males and females

Aspesi

Choleris

2021

J Neuroendocrinology

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Social recognition is an essential skill for the expression of appropriate behaviors towards conspecifics in most social species. Several studies point to oxytocin (OT) and arginine vasopressin (AVP) as key mediators of social recognition in males and females. However, sex differences in social cognitive behaviors highlight an important interplay between OT, AVP and the sex steroids. Estrogens facilitate social recognition by regulating OT action in the hypothalamus and that of OT receptor in the medial amygdala. The role of OT in these brain regions appears to be essential for social recognition in both males and females. Conversely, social recognition in male rats and mice is more dependent on AVP release in the lateral septum than in females. The AVP system comprises a series of highly sexually dimorphic brain nuclei, including the bed nucleus of the stria terminalis, the amygdala and the lateral septum. Various studies suggest that testosterone and its metabolites, including estradiol, influence social recognition in males by modulating the activity of the AVP at V1a receptor. Intriguingly, both estrogens and androgens can affect social recognition very rapidly, through non‐genomic mechanisms. In addition, the androgen metabolites, namely 3α‐diol and 3β‐diol, may also have an impact on social behaviors either by interacting with the estrogen receptors or through other mechanisms. Overall, the regulation of OT and AVP by sex steroids fine tunes social recognition and the behaviors that depend upon it (e.g., social bond, hierarchical organization, aggression) in a sex‐dependent manner. Elucidating the sex‐dependent interaction between sex steroids and neuroendocrine systems is essential for understanding sex differences in the normal and abnormal expression of social behaviors.

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“…2 Expression in memory-related tissues and subcellular distribution of GPER GPER is ubiquitously expressed throughout the body (Prossnitz and Barton, 2011). In addition to peripheral tissues, such as the placenta, reproductive organs, heart, pancreas, and lung (Prossnitz and Barton, 2011), GPER is highly expressed in the CNS (Cooke et al, 2017), including the hippocampus, cortex, hypothalamus, striatum, and amygdala (Brailoiu et al, 2007;Llorente et al, 2020;Marraudino et al, 2021). Recent transcriptomic analysis of adult rats has shown that GPER transcripts are dominant in the brain compared to peripheral tissues and exhibit higher expression levels compared to classical ERs (Hutson et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The effects of GPER on age-associated memory impairment induced by decreased estrogen levels

Luo

Yan

Cao

et al. 2023

Front. Mol. Biosci.

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Estrogen, as a pleiotropic endocrine hormone, not only regulates the physiological functions of peripheral tissues but also exerts vital neuroregulatory effects in the central nervous system (CNS), such as the development of neurons and the formation of neural network connections, wherein rapid estrogen-mediated reactions positively stimulate spinogenesis and regulate synaptic plasticity and synaptic transmission to facilitate cognitive and memory performance. These fast non-genomic effects can be initiated by membrane-bound estrogen receptors (ERs), three best known of which are ERα, ERβ, and G protein-coupled estrogen receptor (GPER). To date, the effects of ERα and ERβ have been well studied in age-associated memory impairment, whereas there is still a lack of attention to the role of GPER in age-associated memory impairment, and there are still disputes about whether GPER indeed functions as an ER to enhance learning and memory. In this review, we provide a systematic overview of the role of GPER in age-associated memory impairment based on its expression, distribution, and signaling pathways, which might bring some inspiration for translational drugs targeting GPER for age-related diseases and update knowledge on the role of estrogen and its receptor system in the brain.

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G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus

Cited by 17 publications

References 91 publications

Panic‐like responses of female Wistar rats confronted by Bothrops alternatus pit vipers, or exposure to acute hypoxia: Effect of oestrous cycle

Panic‐like responses of female Wistar rats confronted by Bothrops alternatus pit vipers, or exposure to acute hypoxia: Effect of oestrous cycle

Neuroendocrine underpinning of social recognition in males and females

The effects of GPER on age-associated memory impairment induced by decreased estrogen levels

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