ArticleAmerican journal of physiology. Endocrinology and metabolism2013
The membrane estrogen receptor ligand STX rapidly enhances GABAergic signaling in NPY/AgRP neurons: role in mediating the anorexigenic effects of 17β-estradiol.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 82 citations in OpenAlex.
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- Estrous cycle modulates fasting-induced torpor propensity via hypothalamic estrogen signalling.Scientific reports · 2026Article
- Direct Intra-Accumbens 17 Beta-Estradiol Administration Increases Voluntary Wheel Running in Ovariectomized Rats.Neuroendocrinology · 2026Article
- Melanocortin-responsive Kiss1 neurons of the arcuate nucleus drive energy expenditure through glutamatergic signaling to the dorsomedial hypothalamus.bioRxiv : the preprint server for biology · 2025Article
- Sexual Dimorphism in Levodopa-Induced Dyskinesia Following Parkinson's Disease: Uncharted Territory.The European journal of neuroscience · 2025Review
- Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways.Frontiers in molecular neuroscience · 2025Article
- Hypothalamic GABAergic neurons: their roles in health and metabolic diseases.Frontiers in endocrinology · 2025Review
- Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins.Journal of endocrinological investigation · 2024Review
- The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause.Frontiers in endocrinology · 2024Review
- Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies.International journal of molecular sciences · 2023Review
- Role of Estrogen Receptor α in Aging and Chronic Disease.Advances in geriatric medicine and research · 2023Article
- The vital role of arcuate nociceptin/orphanin FQ neurones in mounting an oestradiol-dependent adaptive response to negative energy balance via inhibition of nearby proopiomelanocortin neurones.The Journal of physiology · 2022Article
- The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer's disease.Neurobiology of disease · 2022Article
- Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons.Journal of neuroendocrinology · 2022Review
- Hypothalamic Kisspeptin Neurons and the Control of Homeostasis.Endocrinology · 2022Review
- An estrogen-sensitive hypothalamus-midbrain neural circuit controls thermogenesis and physical activity.Science advances · 2022Article
- The PACAP Paradox: Dynamic and Surprisingly Pleiotropic Actions in the Central Regulation of Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Hypothalamic Estrogen Signaling and Adipose Tissue Metabolism in Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Deletion ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Besides its quintessential role in reproduction, 17β-estradiol (E2) is a potent anorexigenic hormone. E2 and the selective Gq-coupled membrane estrogen receptor (Gq-mER) ligand STX rapidly increase membrane excitability in proopiomelanocortin (POMC) neurons by desensitizing the coupling of GABAB receptors to G protein-coupled inwardly rectifying K(+) channels (GIRKs), which upon activation elicit a hyperpolarizing outward current. However, it is unknown whether E2 and STX can modulate GABAB signaling in neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. We used single-cell RT-PCR and whole cell patch clamping with selective pharmacological reagents to show that NPY/AgRP cells of mice express the GABAB-R1 and -R2 receptors and are hyperpolarized by the GABAB agonist baclofen in an E2-dependent manner. In males, E2 rapidly attenuated the coupling of GABAB receptors to GIRKs, which was blocked by the general PI3K inhibitors wortmannin and LY-294002 or the selective p110β subunit inhibitor TGX-221. The ERα-selective agonist propyl pyrazole triol mimicked the effects of E2. STX, in contrast, enhanced the GABAB response in males, which was abrogated by the estrogen receptor (ER) antagonist ICI 182,780. In gonadectomized mice of both sexes, E2 enhanced or attenuated the GABAB response in different NPY/AgRP cells. Coperfusing wortmannin with E2 or simply applying STX always enhanced the GABAB response. Thus, in NPY/AgRP neurons, activation of the Gq-mER by E2 or STX enhances the GABAergic postsynaptic response, whereas activation of ERα by E2 attenuates it. These findings demonstrate a clear functional dichotomy of rapid E2 membrane-initiated signaling via ERα vs. Gq-mER in a CNS neuron vital for regulating energy homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.