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

Krisztina Pohóczky; József Kun; Bálint Szalontai; Éva Szőke; Éva Sághy; Maja Payrits; Béla Kajtár; Krisztina Kovács; József László Környei; János Garai; András Garami; Anikó Perkecz; Levente Czeglédi; Zsuzsanna Helyes

doi:10.1530/JME-15-0184

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

J Mol Endocrinol. 2016 Feb;56(2):135-49. doi: 10.1530/JME-15-0184. Epub 2015 Dec 7.

Affiliations

¹ Department of Pharmacology and PharmacotherapyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryJanos Szentagothai Research CentreUniversity of Pécs, Ifjúság Street 20, H-7624 Pécs, HungaryDepartments of PathologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of PhysiologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of Pathophysiology and GerontologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryMTA-PTE NAP B Chronic Pain Research GroupHungary, Szigeti Street 12, H-7624 Pécs, HungaryInstitute of Animal ScienceCentre for Agricultural and Applied Economic Sciences, University of Debrecen, PO Box 36, H-4015 Debrecen, Hungary Department of Pharmacology and PharmacotherapyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryJanos Szentagothai Research CentreUniversity of Pécs, Ifjúság Street 20, H-7624 Pécs, HungaryDepartments of PathologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of PhysiologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of Pathophysiology and GerontologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryMTA-PTE NAP B Chronic Pain Research GroupHungary, Szigeti Street 12, H-7624 Pécs, HungaryInstitute of Animal ScienceCentre for Agricultural and Applied Economic Sciences, University of Debrecen, PO Box 36, H-4015 Debrecen, Hungary.
² Department of Pharmacology and PharmacotherapyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryJanos Szentagothai Research CentreUniversity of Pécs, Ifjúság Street 20, H-7624 Pécs, HungaryDepartments of PathologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of PhysiologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of Pathophysiology and GerontologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryMTA-PTE NAP B Chronic Pain Research GroupHungary, Szigeti Street 12, H-7624 Pécs, HungaryInstitute of Animal ScienceCentre for Agricultural and Applied Economic Sciences, University of Debrecen, PO Box 36, H-4015 Debrecen, Hungary Department of Pharmacology and PharmacotherapyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryJanos Szentagothai Research CentreUniversity of Pécs, Ifjúság Street 20, H-7624 Pécs, HungaryDepartments of PathologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of PhysiologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of Pathophysiology and GerontologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryMTA-PTE NAP B Chronic Pain Research GroupHungary, Szigeti Street 12, H-7624 Pécs, HungaryInstitute of Animal ScienceCentre for Agricultural and Applied Economic Sciences, University of Debrecen, PO Box 36, H-4015 Debrecen, Hungary Department of Pharmacology and PharmacotherapyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryJanos Szentagothai Research CentreUniversity of Pécs, Ifjúság Street 20, H-7624 Pécs, HungaryDepartments of PathologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of PhysiologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of Pathophysiology and Ger
³ Department of Pharmacology and PharmacotherapyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryJanos Szentagothai Research CentreUniversity of Pécs, Ifjúság Street 20, H-7624 Pécs, HungaryDepartments of PathologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of PhysiologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryDepartment of Pathophysiology and GerontologyUniversity of Pécs Medical School, Szigeti Street 12, H-7624 Pécs, HungaryMTA-PTE NAP B Chronic Pain Research GroupHungary, Szigeti Street 12, H-7624 Pécs, HungaryInstitute of Animal ScienceCentre for Agricultural and Applied Economic Sciences, University of Debrecen, PO Box 36, H-4015 Debrecen, Hungary.

PMID: 26643912
DOI: 10.1530/JME-15-0184

Abstract

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 [Ca(2+)]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.

Keywords: estrogen; fluorescent calcium imaging; immunohistochemistry; mRNA expression; macrophage migration inhibitory factor; progesterone; rat endometrium; transient receptor potential ankyrin 1 and vanilloid 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Endometrium / metabolism*
Estrogens / physiology*
Female
Gene Expression
Intramolecular Oxidoreductases / genetics
Intramolecular Oxidoreductases / metabolism
Macrophage Migration-Inhibitory Factors / genetics
Macrophage Migration-Inhibitory Factors / metabolism
Nitric Oxide Synthase Type II / genetics
Nitric Oxide Synthase Type II / metabolism
Primary Cell Culture
Rats, Wistar
TRPA1 Cation Channel
TRPC Cation Channels / genetics
TRPC Cation Channels / metabolism*
TRPV Cation Channels / genetics
TRPV Cation Channels / metabolism*
Transcriptional Activation
Up-Regulation

Substances

Estrogens
Macrophage Migration-Inhibitory Factors
TRPA1 Cation Channel
TRPC Cation Channels
TRPV Cation Channels
Trpa1 protein, rat
Trpv1 protein, rat
Nitric Oxide Synthase Type II
Nos2 protein, rat
Intramolecular Oxidoreductases
Mif protein, rat