Treatment of acromegaly by rosiglitazone via upregulating 15-PGDH in both pituitary adenoma and liver.
Cancer
Human specimen
Medicine
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
24 Sep 2021
24 Sep 2021
Historique:
received:
04
05
2021
revised:
26
07
2021
accepted:
11
08
2021
entrez:
6
9
2021
pubmed:
7
9
2021
medline:
7
9
2021
Statut:
epublish
Résumé
Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver.
Identifiants
pubmed: 34485865
doi: 10.1016/j.isci.2021.102983
pii: S2589-0042(21)00951-2
pmc: PMC8403734
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102983Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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