Evidence map›Paper›PMID 34467411›Full record

ArticleThe Journal of clinical endocrinology and metabolism2022

Pituitary Somatotroph Adenoma-derived Exosomes: Characterization of Nonhormonal Actions.

Cuiqi Zhou, Stephen Shen, Rosemary Moran, Nan Deng, Eduardo Marbán, Shlomo Melmed

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Cuiqi ZhouDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Stephen ShenDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Rosemary MoranDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Nan DengBiostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Eduardo MarbánSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Shlomo MelmedDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.ORCID 0000-0002-2355-3447
Cedars-Sinai Medical Center · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Mechanisms for GH action on epithelial cellsR01DK113998 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI SHLOMO MELMED · 2018 to 2026
$3.0M
NCATS NIH HHS UL1 TR001881NCATS NIH HHS UL1TR001881NIDDK NIH HHS R01 DK113998NIH HHS R01DK113998
6 · The paper itself

Abstract

contextThe identification and biological actions of pituitary-derived exosomes remain elusive.

objectiveThis work aimed to validate production of exosomes derived from human and rat pituitary and elucidate their actions.

methodsIsolated extracellular vesicles (EVs) were analyzed by Nanoparticle Tracking Analysis (NTA) and expressed exosomal markers detected by Western blot, using nonpituitary fibroblast FR and myoblast H9C2 cells as controls. Exosome inhibitor GW4869 was employed to detect attenuated EV release. Exosomal RNA contents were characterized by RNA sequencing. In vitro and in vivo hepatocyte signaling alterations responding to GH1-derived exosomes (GH1-exo) were delineated by mRNA sequencing. GH1-exo actions on protein synthesis, cAMP (3',5'-cyclic adenosine 5'-monophosphate) response, cell motility, and metastases were assessed.

resultsNTA, exosomal marker detection, and GW4869 attenuated EV release, confirming the exosomal identity of pituitary EVs. Hydrocortisone increased exosome secretion in GH1 and GH3 cells, suggesting a stress-associated response. Exosomal RNA contents showed profiles distinct for pituitary cells, and rat primary hepatocytes exposed to GH1-exo exhibited transcriptomic alterations distinct from those elicited by growth hormone or prolactin. Intravenous GH1-exo injection into rats attenuated hepatic Eif2ak2 and Atf4 mRNA expression, both involved in cAMP responses and amino acid biosynthesis. GH1-exo suppressed protein synthesis and forskolin-induced cAMP levels in hepatocytes. GH1-exo-treated HCT116 cells showed dysregulated p53 and mitogen-activated protein kinase (MAPK) pathways and attenuated motility of malignant HCT116 cells, and decreased tumor metastases in nude mice harboring splenic HCT116 implants.

conclusionOur findings elucidate biological actions of somatotroph-derived exosomes and implicate exosomes as nonhormonal pituitary-derived messengers.

Indexed as

AdenomaAdultAniline CompoundsAnimalsBenzylidene CompoundsCell CommunicationCoculture TechniquesExosomesFemaleGrowth Hormone-Secreting Pituitary AdenomaHepatocytesHumansMalePituitary GlandPrimary Cell CultureRatsAniline CompoundsBenzylidene CompoundsGW 4869exosomenonhormonal actionspituitary somatotroph adenoma

Identifiers

PMID34467411
PMCPMC8764361
OpenAlexW3196818169

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.