雌激素依赖性上调大鼠子宫内膜中TRPA1和TRPV1受体蛋白。
Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium.
作者信息
Pohóczky Krisztina, Kun József, Szalontai Bálint, Szőke Éva, Sághy Éva, Payrits Maja, Kajtár Béla, Kovács Krisztina, Környei József László, Garai János, Garami András, Perkecz Anikó, Czeglédi Levente, Helyes Zsuzsanna
机构信息
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 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
出版信息
J Mol Endocrinol. 2016 Feb;56(2):135-49. doi: 10.1530/JME-15-0184. Epub 2015 Dec 7.
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.
瞬时受体电位锚蛋白1（TRPA1）和香草酸受体1（TRPV1）主要在感觉神经中表达，可被炎症刺激激活，并介导炎症和疼痛。尽管它们已在人子宫内膜中被发现，但其调节机制和功能尚不清楚。因此，我们研究了它们在大鼠子宫内膜中雌激素和孕酮依赖性的变化，并与雌激素调节的炎症细胞因子巨噬细胞移动抑制因子（MIF）进行比较。对四周龄（性未成熟）和四月龄（性成熟）雌性大鼠分别给予非选择性雌激素受体（ER）激动剂己烯雌酚（DES）、孕酮及其组合进行处理，或进行卵巢切除。分别采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法测定mRNA和蛋白表达水平。通过对培养的原代大鼠子宫内膜细胞进行比率法[Ca(2+)]i测量来研究通道功能。在子宫内膜中检测到TRP受体和MIF的mRNA和蛋白水平，且它们的定位相似。在未成熟上皮细胞中观察到免疫染色，而在成年大鼠中观察到基质、腺体和上皮细胞呈阳性。通过激活诱导的钙内流显示功能性活性TRP受体蛋白存在于子宫内膜细胞中。在成年大鼠中，DES处理后Trpa1和Trpv1 mRNA水平显著上调。每次处理后TRPA1均增加，但联合处理和卵巢切除后TRPV1保持不变。在未成熟大鼠中，DES处理导致两种通道的mRNA表达增加以及TRPV1免疫阳性率升高。在大多数情况下，MIF表达与TRPA1/TRPV1平行变化。DES上调了子宫内膜细胞培养物中Trpa1、Trpv1和Mif mRNA水平，但具有ERα选择性效力的17β-雌二醇仅增加了Trpv1的表达。我们首次提供了TRPA1/TRPV1在大鼠子宫内膜中的表达及其雌激素诱导上调与MIF相关的证据。
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