Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

    1. Zsuzsanna Helyes1,2,6
    1. 1Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Szigeti Street 12, H‐7624 Pécs, Hungary
      2Janos Szentagothai Research Centre, University of Pécs, Ifjúság Street 20, H‐7624 Pécs, Hungary
      3Departments of Pathology, University of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, Hungary
      4Department of Physiology, University of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, Hungary
      5Department of Pathophysiology and Gerontology, University of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, Hungary
      6MTA‐PTE NAP B Chronic Pain Research Group, Hungary, Szigeti Street 12, H‐7624 Pécs, Hungary
      7Institute of Animal Science, Centre for Agricultural and Applied Economic Sciences, University of Debrecen, PO Box 36, H‐4015 Debrecen, Hungary
    1. Correspondence should be addressed to Zs Helyes; Email: zsuzsanna.helyes{at}


    Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors expressed predominantly in sensory nerves are activated by inflammatory stimuli and mediate inflammation and pain. Although they have been shown in the human endometrium, their regulation and function are unknown. Therefore, we investigated their estrogen- and progesterone-dependent alterations in the rat endometrium in comparison with the estrogen-regulated inflammatory cytokine macrophage migration inhibitory factor (MIF). Four-week-old (sexually immature) and four-month-old (sexually mature) female rats were treated with the non-selective estrogen receptor (ER) agonist diethylstilboestrol (DES), progesterone and their combination, or ovariectomized. RT-PCR and immunohistochemistry were performed to determine mRNA and protein expression levels respectively. Channel function was investigated with ratiometric [Ca2+]i measurement in cultured primary rat endometrial cells. Both TRP receptors and MIF were detected in the endometrium at mRNA and protein levels, and their localizations were similar. Immunostaining was observed in the immature epithelium, while stromal, glandular and epithelial positivity were observed in adults. Functionally active TRP receptor proteins were shown in endometrial cells by activation-induced calcium influx. In adults, Trpa1 and Trpv1 mRNA levels were significantly up-regulated after DES treatment. TRPA1 increased after every treatment, but TRPV1 remained unchanged following the combined treatment and ovariectomy. In immature rats, DES treatment resulted in increased mRNA expression of both channels and elevated TRPV1 immunopositivity. MIF expression changed in parallel with TRPA1/TRPV1 in most cases. DES up-regulated Trpa1, Trpv1 and Mif mRNA levels in endometrial cell cultures, but 17β-oestradiol having ERα-selective potency increased only the expression of Trpv1. We provide the first evidence for TRPA1/TRPV1 expression and their estrogen-induced up-regulation in the rat endometrium in correlation with the MIF.

    • Revision received 3 December 2015
    • Accepted 4 December 2015
    • Made available online as an Accepted Preprint 7 December 2015
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