Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice

Hart, David; Nilges, Mary; Pollard, Kevin; Lynn, Tucker; Patsos, Olivia P; Shiel, Cassidy; Clark, Sara; Vasudevan, Nandini

doi:10.1016/j.steroids.2013.11.004

Cited by 46 publications

(33 citation statements)

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“…However, this conclusion is complicated by two other recent reports that suggest a role for GPER in the modulatory effects of E 2 in the dorsal hippocampus. In one study, repeated systemic administration of G-1 had no effect on either ERK isoform in the dorsal hippocampus of gonadectomized male mice, but increased dorsal hippocampal ERK1/2 activation in gonadectomized female mice (Hart et al 2014). Another recent study found that bath-applied G-15 prevented E 2 from increasing postsynaptic strength and phosphorylation of ERK1/2 in hippocampal slices from ovariectomized mice, suggesting a key role of GPER in mediating the effects of E 2 (Kumar et al 2015).…”

Section: Receptorsmentioning

confidence: 99%

“…More recently, deletion of ERa in mice impaired social recognition memory among females, but not males (Sánchez-Andrade and Kendrick 2011), suggesting sex differences in the role of ERa in multiple forms of memory. No studies to date have examined sex differences in the role of GPER in memory, but one recent study found that systemic administration of G-1 reduced anxiety in gonadectomized male, but not female, mice (Hart et al 2014). As noted above, this study also found that G-1 increased dorsal hippocampal ERK1/2 activation in females, but not in males (Hart et al 2014).…”

Section: Receptorsmentioning

confidence: 99%

“…No studies to date have examined sex differences in the role of GPER in memory, but one recent study found that systemic administration of G-1 reduced anxiety in gonadectomized male, but not female, mice (Hart et al 2014). As noted above, this study also found that G-1 increased dorsal hippocampal ERK1/2 activation in females, but not in males (Hart et al 2014). In models of ischemic or hypoxic brain injury, GPER activation appears to be more beneficial for females than for males (Murata et al 2013;Broughton et al 2014).…”

Section: Receptorsmentioning

confidence: 99%

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Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

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Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17b-estradiol (E 2 ), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E 2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E 2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E 2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs.Hormones have long been known to play key roles in regulating learning and memory. Many hormones, including epinephrine, glucocorticoids, and insulin influence learning and memory via inverted U-shaped dose-response relationships in which memory is enhanced by moderate, but not low or high, hormone levels (Roozendaal 2000;Korol and Gold 2007;McNay and Recknagel 2011). Research from the past two decades has demonstrated that sex steroid hormones, particularly the potent estrogen 17b-estradiol (E 2 ), also regulate learning and memory in male and female rodents via an inverted U-shaped dose-response function that is influenced by estrogen receptor expression (Packard and Teather 1997a;Packard 1998;Foster 2012). Yet E 2 has not gained widespread acceptance as a hormonal modulator of memory in both females and males, perhaps because the majority of this research has been conducted in female rodents. Moreover, the common view of E 2 as a "female" hormone may contribute to the misperception that E 2 is not relevant for cognitive function in males. However, considerable evidence supports a vital role for E 2 in mediating neural function and behavior in male rodents. Therefore, it is important for investigators working with males to understand the ways in which E 2 and other sex steroid hormones (e.g., androgens, progestins, and other estrogens) may influence their brain regions and behaviors of interest.Another reason for investigators to be cognizant of sex steroid hormone-induced regulation of learning and memory is that males and females may respond differently to various treatments and environmental factors. A classic example is that of acute stress, which enhances classical conditioning and increases apical CA1 dendritic spine density in male rats, but impairs classical conditioning and decreases CA1 spine density in female rats (Wood and Shors 1998;Shors et al. 2001). Therefore, investigators hoping to comply with National Institutes of Health policies that encourage the inclusion of females in biomedical research must be aware that adding females to a study is not as simple as adding another group. In some ways, females are fundamentally different from males, the most obvious of which is the presence of reproductive...

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Section: Receptorsmentioning

confidence: 99%

Section: Receptorsmentioning

confidence: 99%

Section: Receptorsmentioning

confidence: 99%

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Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

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“…Previous studies have shown an effect of chronic or acute administration of G-1 on nonsocial behaviors such as learning and memory [62] and anxiety [40,55] in female and male rodents. Here, we show that GPR30 activation is sufficient to drive a classic 17β-estradiol-regulated reproductive social behavior, lordosis, in female mice.…”

Section: Resultsmentioning

confidence: 99%

“…Since GPR30 activation is sufficient and ERα appears to be necessary for lordosis behavior in female mice, the molecular mechanism of GPR30 activation of lordosis may require the presence of ERα. GPR30 activation could be upstream of ERα action; our previous study showed that G-1 can phosphorylate ERα at serine 118, albeit in males in the ventral hippocampus [55]. In the mouse spermatogonial cell line GC-1, transcription of the c-fos gene and ERK1/2 activation by 17β-estradiol requires both ERα and GPR30, since these were sensitive to the ER-reducing inhibitor, ICI 182780, as well as to an siRNA to GPR30 [56].…”

Section: Discussionmentioning

confidence: 99%

Activation of the GPR30 Receptor Promotes Lordosis in Female Mice

Anchan

Gafur²,

Sato³

et al. 2014

Neuroendocrinology

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Background/Aims: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior as well as kinase cascades activated by this receptor, led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents. Method: In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm prior to testing with stud males. Results: As expected, 17β-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects. Conclusion: This study demonstrates that activation of the mER GPR30 stimulates social behavior in a rodent model in a manner similar to EB.

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Immunoblot Detection of the Phosphorylation of the Estrogen Receptor α as an Outcome of GPR30/GPER1 Activation

Clark

Pollard

Rainville

et al. 2022

Methods in Molecular Biology

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Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice

Cited by 46 publications

References 50 publications

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Activation of the GPR30 Receptor Promotes Lordosis in Female Mice

Immunoblot Detection of the Phosphorylation of the Estrogen Receptor α as an Outcome of GPR30/GPER1 Activation

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