ABSTRACT
As prolactinomas fail to respond to dopamine agonist (DA) in 10-20% of cases, we hypothesized that somatostatin subtype 2 receptor (sst2) overexpression in DA-resistant prolactinomas may enhance suppression of prolactine (PRL) using chimeric agonist (dopastatin) that simultaneously binds sst2 and the dopamine subtype 2 receptor (D2DR).
DESIGN AND METHODS:
PRL suppression by octreotide, sst5 agonist, sst2-D2DR agonist (BIM-23A760 dopastatin) and cabergoline was assessed in primary cultures of seven DA-resistant prolactinomas overexpressing sst2.
RESULTS:
sst2 was effectively overexpressed via adenoviral expression in prolactinomas (38.1±7.4 vs. 0.1±0.1 copy/copy β-Gus) and induced octreotide sst2-mediated PRL suppression that remained lower than that induced by DA. BIM-23A760 inhibited PRL similarly to cabergoline both in the control and sst2-expressing cells. Antagonist experiments confirmed predominant dopaminergic effect in dopastatin activity.
CONCLUSION:
sst2 was successfully overexpressed in prolactinomas. However BIM-23A760 was unable to
Somatostatin receptor sst2 gene transfer in human prolactinomas in vitro: impact on sensitivity to dopamine, somatostatin and dopastatin, in the control of prolactin secretion
Riferimento:
Mol Cell Endocrinol. 2012 May 15;355(1):106-13.
Autori:
Cuny T, Mohamed A, Graillon T, Roche C, Defilles C, Germanetti AL, Couderc B, Figarella- Branger D, Enjalbert A, Barlier A, Saveanu A.
Fonte:
Mol Cell Endocrinol. 2012 May 15;355(1):106-13.
Anno:
2012
Azione:
Il recettore, sottotipo 2, della somatostatina (sst2) è sovra-espresso con successo nei
prolattinomi.
Target:
Recettore, sottotipo 2, della somatostatina/prolattinoma.
Sostanze: