CoChat
Sign Up
Cited by 62Hypothalamic control of reproductive hormonesReproductive Biology and FertilityProtein Kinase Regulation and GTPase Signaling

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Gonadotropin-releasing hormone activates mitogen-activated protein kinase in human ovarian and placental cells

Keun Kang, Sung, Tai, Chen-Jei, Wa Cheng, Kwai, Leung, Peter C.K·2000·Molecular and Cellular Endocrinology
DOI 10.1016/s0303-7207(00)00320-8
Open this paper in CoChat — free account

Abstract

Considering that the action of gonadotropin-releasing hormone (GnRH) may be mediated via different signaling pathways in extrapituitary tissues, in the present study we investigated the role of the human GnRH receptor (GnRHR) in activating mitogen-activated protein kinases (MAPKs), which regulate cell growth, division, and differentiation. The phosphorylation state of p44 and p42 MAPKs was examined using antibodies that distinguish phospho-p44/42 MAPK (P-MAPK, Thr(202)/Tyr(204)) from total p44/42 MAPK (T-MAPK, activated plus inactivated) in human ovarian and placental cells. Cell cultures were treated with various concentrations of a GnRH agonist, (D-Ala(6))-GnRH, for 5 min. (D-Ala(6))-GnRH stimulated a rapid activation of P-MAPK in human granulosa-luteal cells (hGLCs) and immortalized extravillous trophoblast (IEVT) cells. Interestingly, (D-Ala(6))-GnRH treatment of ovarian cancer (OVCAR-3) and placental carcinoma (JEG-3) cells induced a biphasic regulatory pattern in P-MAPK activity. In contrast, no change of T-MAPK levels was observed following addition of the GnRH agonist in the ovarian and placental cells examined. The physiological implication of MAPK activation by GnRH in the ovarian and placental cells was also investigated. Human GLCs were treated with (D-Ala(6))-GnRH for 24 h, and progesterone secretion was measured by an established RIA. (D-Ala(6))-GnRH induced a significant decrease in progesterone secretion with maximum inhibition (a 45% decrease over basal level) at 10(-7) M. This inhibitory effect was completely reversed by pretreatment with MAPK/ERK kinase 1 (MEK1) inhibitor (PD98059), suggesting the involvement of the MAPK pathway in hGLCs. Placental JEG-3 cells were treated with (D-Ala(6))-GnRH for 24 h, and betahCG mRNA level was measured using Northern blot analysis. (D-Ala(6))-GnRH stimulated the expression of betahCG mRNA to 160% of control value in JEG-3 cells. In contrast to the ovarian cells, pretreatment of JEG-3 cells with PD98059 failed to block the stimulatory effect of GnRH on betahCG mRNA level, suggesting that other signaling pathway(s) may play a more dominant role in GnRH-induced betahCG mRNA expression. To our knowledge, this is the first demonstration that (1) GnRH induces activation of the MAPK signaling pathway in normal and carcinoma cells of the human ovary and placenta, and (2) MAPK mediates the direct action of GnRH on progesterone production in hGLCs.

Overview

Integrity signals

Registry

Crossref · 10.1016/s0303-7207(00)00320-8

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Metadata

Authors
Keun Kang, S., Tai, C.-J., Wa Cheng, K., & Leung, P. C. K.
Affiliations
University of British Columbia (CA)
Corresponding author
Leung, Peter C.K
ORCID
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2000-12-25
Volume
170
Issue
1-2
Pages
143-151
ISSN
0303-7207 (ISSN-L)
DOI
10.1016/s0303-7207(00)00320-8
OpenAlex
W1964586431
Cited by
62
References
42
Citations by year
2024: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2012: 1
FWCI
5.83
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Research Council
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
gonadotropin-releasing hormone, GnRH receptor, mitogen-activated protein kinase, ERK signaling, granulosa-lutein cells, extravillous trophoblast, progesterone secretion, GnRH agonist, MEK1 inhibition, ovarian cancer cells
MeSH terms
Animals, Dose-Response Relationship, Drug, Female, Chorionic Gonadotropin, Humans, Gonadotropin-Releasing Hormone, Ovary, Pituitary Gland, Placenta, Progesterone, RNA, Messenger, Trophoblasts, Tumor Cells, Cultured, Immunoblotting, Mitogen-Activated Protein Kinases, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review