Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells.
Acromegaly
Cabergoline
Dopastatin
Octreotide
TBR-065
Journal
Pituitary
ISSN: 1573-7403
Titre abrégé: Pituitary
Pays: United States
ID NLM: 9814578
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
accepted:
17
11
2020
pubmed:
13
1
2021
medline:
15
12
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
Somatostatin (SST) and dopamine (DA) inhibit growth hormone (GH) secretion and proliferation of GH-secreting pituitary adenomas (GHomas) through binding to SSTR2 and D2R receptors. Chimeric SST-DA compounds (Dopastatins) display increased potency in inhibiting GH secretion, as compared with individual SST or DA analogs (alone or combined). To assess the efficacy of a second-generation dopastatin, TBR-065, in suppressing GH secretion from human GH- and GH/prolactin(PRL)-omas. We compared the ability of TBR-065 to inhibit GH secretion from primary cultures of human GH- or GH/PRLoma cells to that of the first generation dopastatin, TBR-760 (formerly BIM-23A760), octreotide (OCT) and cabergoline (CAB), the later either alone or combined. We investigated whether there was any impact of BIM-133, the metabolite of TBR-065, on the ability of TBR-065 to inhibit GH in these cultures. 17 GH- and GH/PRLomas were included in this study. Inhibition of GH secretion by TBR-065, TBR-760, OCT and CAB (0.1 pM to 0.1 µM) was assessed over a period of 8 h. All tumors expressed SSTR2 and D2R mRNAs. GH suppression was higher with TBR-065 as compared with TBR-760 (E TBR-065 has significantly improved efficacy in suppressing GH secretion as compared to current available therapies and may represent a new promising option for the treatment of acromegaly.
Identifiants
pubmed: 33433890
doi: 10.1007/s11102-020-01113-4
pii: 10.1007/s11102-020-01113-4
doi:
Substances chimiques
Receptors, Dopamine D2
0
Receptors, Somatostatin
0
Human Growth Hormone
12629-01-5
Somatostatin
51110-01-1
Cabergoline
LL60K9J05T
Octreotide
RWM8CCW8GP
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
351-358Références
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