Cited by 70Neuropeptides and Animal PhysiologyHypothalamic control of reproductive hormonesEstrogen and related hormone effects

Tachykinin Receptor and Neutral Endopeptidase Gene Expression in the Rat Uterus: Characterization and Regulation in Response to Ovarian Steroid Treatment*

Pinto, Francisco M., Armesto, Cristina P., Magraner, Josefina, Trujillo, Mar, MartÍn, Julio D., Luz Candenas, M.·1999·Endocrinology

Abstract

Tachykinin neuropeptides, such as substance P, are localized to a population of sensory fibers that innervate the mammalian female reproductive tract. In the present study, we have characterized tachykinin NK1 receptor (NK1R), NK2 receptor (NK2R), and NK3 receptor (NK3R) gene expression by semiquantitative RT-PCR in uteri from ovariectomized rats and studied their regulation in response to 17beta-estradiol (E2), progesterone (P4), or a combination of both. In addition, we analyzed the expression and regulation of the neutral endopeptidase 24.11 (NEP), the most important enzyme involved in tachykinin degradation in the rat uterus. In uteri from control (olive oil-treated) rats, RT-PCR assays revealed single bands corresponding to the expected product sizes encoding complementary DNA for NK1R (232 bp), NK2R (491 bp), NK3R (325 bp), and NEP (221 bp). The identity of the amplified fragments was confirmed by DNA sequence analysis. Compared with control rats, NK1R messenger RNA (mRNA) was increased by 2-fold in uteri from rats treated with E2, was decreased by 3.3-fold in rats treated with P4, and was decreased by 1.8-fold in rats treated with both E2 and P4. Uterine NK2R mRNA levels were not altered by any steroid treatment. E2 treatment decreased by 15-fold NK3R mRNA. P4 was without effect if administered alone and did not influence the E2-induced decrease in NK3R mRNA. NEP mRNA levels were about 4-fold lower in E2-treated than in P4-treated rats. Functional studies were carried out in uteri from E2- or P4-treated ovariectomized rats to characterize the contractile response evoked by the selective tachykinin receptor agonists [Sar9Met(O2)11]substance P (NK1R selective), [Nle10]NKA-(4-10) (NK2R selective), and [MePhe7]NKB (NK3R selective) in the presence of the NEP inhibitor phosphoramidon (1 microM). A marked correlation was observed between the magnitude of the contractile response to each agonist and the level of expression determined by RT-PCR for each tachykinin receptor. The present findings show that tachykinin NK1R, NK2R, NK3R, and NEP are expressed in the rat uterus and that ovarian steroids differentially regulate their expression.

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Crossref · 10.1210/endo.140.6.6695

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Authors
Pinto, F. M., Armesto, C. P., Magraner, J., Trujillo, M., MartÍn, J. D., & Luz Candenas, M.
Affiliations
  • Universidad de La Laguna (ES)
  • Centro de Investigaciones Científicas Isla de La Cartuja, Instituto de Investigaciones Químicas, 41092 Sevilla, Spain; and Departamento de Genética, Facultad de Biología, Universidad de La Laguna, 38206 Tenerife, Spain
Corresponding author
Pinto, Francisco M.
Venue
Endocrinology
Published
1999-06-01
Volume
140
Issue
6
Pages
2526-2532
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2105604596
Cited by
70
References
40
Citations by year
2022: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 5
FWCI
1.81
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Generalitat Valenciana
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
tachykinin receptors, neurokinin-1 receptor, NK2 receptor, NK3 receptor, neutral endopeptidase 24.11, uterus, estradiol, progesterone, ovarian steroids, gene expression regulation, substance P, neurokinin A, neurokinin B, phosphoramidon, uterine contractility, ovariectomized rats
MeSH terms
Animals, Female, Gene Expression Regulation, RNA, Messenger, Gonadal Steroid Hormones, Uterus, Neprilysin, Rats, Wistar, Receptors, Tachykinin, Reverse Transcriptase Polymerase Chain Reaction, Rats

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