ArticleInternational journal of molecular sciences2021
Partial Agonistic Actions of Sex Hormone Steroids on TRPM3 Function.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- TRPM3 activation causes CGRP release in trigeminal neurons: Implications for migraine mechanisms.Headache · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- The ExPAND Study: A Prospective Association Study into Endometriosis-Associated Pain, Neurosteroid Synthesis, and TRPM3.Biomolecules · 2025Article
- Phenotype Spectrum of TRPM3-Associated Disorders.Annals of neurology · 2025Article
- Sex difference in TRPM3 channel functioning in nociceptive and vascular systems: an emerging target for migraine therapy in females?The journal of headache and pain · 2025Review
- Sexual Dimorphism in Migraine. Focus on Mitochondria.Current pain and headache reports · 2025Review
- Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.Frontiers in molecular biosciences · 2025Article
- TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels.The journal of physiological sciences : JPS · 2024Review
- The TRPA1 Ion Channel Mediates Oxidative Stress-Related Migraine Pathogenesis.Molecules (Basel, Switzerland) · 2024Review
- TRPM channels in health and disease.Nature reviews. Nephrology · 2024Review
- A Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens.Cells · 2024Article
- Novel characterization of endogenous transient receptor potential melastatin 3 ion channels from Gulf War Illness participants.PloS one · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Sex hormone steroidal drugs were reported to have modulating actions on the ion channel TRPM3. Pregnenolone sulphate (PS) presents the most potent known endogenous chemical agonist of TRPM3 and affects several gating modes of the channel. These includes a synergistic action of PS and high temperatures on channel opening and the PS-induced opening of a noncanonical pore in the presence of other TRPM3 modulators. Moreover, human TRPM3 variants associated with neurodevelopmental disease exhibit an increased sensitivity for PS. However, other steroidal sex hormones were reported to influence TRPM3 functions with activating or inhibiting capacity. Here, we aimed to answer how DHEAS, estradiol, progesterone and testosterone act on the various modes of TRPM3 function in the wild-type channel and two-channel variants associated with human disease. By means of calcium imaging and whole-cell patch clamp experiments, we revealed that all four drugs are weak TRPM3 agonists that share a common steroidal interaction site. Furthermore, they exhibit increased activity on TRPM3 at physiological temperatures and in channels that carry disease-associated mutations. Finally, all steroids are able to open the noncanonical pore in wild-type and DHEAS also in mutant TRPM3. Collectively, our data provide new valuable insights in TRPM3 gating, structure-function relationships and ligand sensitivity.
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