ArticleeNeuro
The Progestin Receptor Interactome in the Female Mouse Hypothalamus: Interactions with Synaptic Proteins Are Isoform Specific and Ligand Dependent.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Progesterone receptors regulate susceptibility to spreading depression.Experimental neurology · 2025Article
- Progesterone Receptor Activation Regulates Sensory Sensitivity and Migraine Susceptibility.The journal of pain · 2024Article
- Cannabinoid receptor type 1 (CBiScience · 2023Article
- A New Player in Depression: MiRNAs as Modulators of Altered Synaptic Plasticity.International journal of molecular sciences · 2022Review
- The Prominent Role of the Temporal Lobe in Premenstrual Syndrome and Premenstrual Dysphoric Disorder: Evidence From Multimodal Neuroimaging.Frontiers in psychiatry · 2022Review
- Article
- Sex and age influence gonadal steroid hormone receptor distributions relative to estrogen receptor β-containing neurons in the mouse hypothalamic paraventricular nucleus.The Journal of comparative neurology · 2021Article
- Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer.Scientific data · 2021Article
- Reverse-Phase Protein Array: Technology, Application, Data Processing, and Integration.Journal of biomolecular techniques : JBT · 2021Article
- Progesterone modulates neuronal excitability bidirectionally.Neuroscience letters · 2021Review
- Dopamine-induced interactions of female mouse hypothalamic proteins with progestin receptor-A in the absence of hormone.Journal of neuroendocrinology · 2020Article
- Progesterone for the treatment of central nervous system disorders: the many signaling roads for a single molecule.Neural regeneration research · 2020Article
- Human menstrual cycle variation in subcortical functional brain connectivity: a multimodal analysis approach.Brain structure & function · 2020Article
- Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase-tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I-positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease.
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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.