Evidence map›Paper›PMID 12925744›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2003

Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling.

Jon Nilsen, Roberta Diaz Brinton

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 5 pooled it
10.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 5 syntheses or guidelines pooled it, 246 citations in OpenAlex.

  1. Pooled it
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  12. Biological Sex Disparities in Alzheimer's Disease.Current topics in behavioral neurosciences · 2025
    Review
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  18. Cognitive Changes with Reproductive Aging, Perimenopause, and Menopause.Obstetrics and gynecology clinics of North America · 2018
    Review
  19. Article
  20. Article

44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Jon NilsenDepartment of Molecular Pharmacology and Toxicology and Program in Neuroscience, Pharmaceutical Sciences Center, University of Southern California, Los Angeles, CA 90089, USA. rbrinton@hsc.usc.edu
Roberta Diaz Brinton
University of Southern California · US

Funding

NIA NIH HHS P01 AG1475
6 · The paper itself

Abstract

The impact of progestins on estrogen-inducible mechanisms of neuroprotection was investigated. Previously, we showed that estrogen and progesterone are neuroprotective against excitotoxicity, whereas the synthetic progestin medroxyprogesterone acetate (MPA; Provera) is not. Here, we demonstrate that 17beta-estradiol (E2) and progesterone (P4) treatment of hippocampal neurons attenuated the excitotoxic glutamate-induced rise in intracellular calcium concentration. Although MPA had no effect alone, MPA completely antagonized E2-induced attenuation of intracellular calcium concentration. Activation of extracellular receptor kinase (ERK) is required for estrogen-induced neuroprotection and calcium regulation. Paradoxically, E2, P4, and MPA all elicited similar rapid and transient activation of ERK, presenting a contradiction between the dependence on ERK for gonadal hormone-induced neuroprotection and the lack of neuroprotection induced by MPA. Subcellular analysis of ERK demonstrated that the phospho-ERK signal is transduced to the nucleus only by E2 and P4, not by MPA. These results indicate that the profile of nuclear translocation of ERK is consistent with the neuroprotective profile. Further, the E2-induced nuclear translocation of ERK was blocked by coadministration of MPA. Results of this study reveal that nuclear ERK induction by ovarian steroids is predictive of the neuroprotective effects of estrogen and progestin treatments, revealing a hitherto unrecognized divergence of progestin signaling through the src/MAPK pathway. These results have much broader implications encompassing the impact of progestins on estrogen-mediated effects in multiple tissues. The recent results from the Women's Health Initiative trial, which used MPA as the progestinal agent, indicate that differences between progestin formulations are crucial to health outcomes in women.

Indexed as

AnimalsCalciumEstradiolGlutamic AcidHippocampusHormone Replacement TherapyMAP Kinase Signaling SystemMedroxyprogesterone AcetateProgesteroneRatsCalciumEstradiolGlutamic AcidMedroxyprogesterone AcetateProgesterone

Identifiers

PMID12925744
PMCPMC193591
OpenAlexW2069327573

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.