Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 S11.2 | DOI: 10.1530/endoabs.32.S11.2

ECE2013 Symposia New mechanisms in SST analogue response (3 abstracts)

Role of filamin A in dopamine and somatostatin receptor targeting in the pituitary

Erika Peverelli


University of Milan, IRCCS Osp Maggiore Policlinico, Milan, Italy.


Molecular mechanisms underlying resistance of pituitary tumors to somatostatin (SS) and dopamine (DA) analogs treatment are not completely understood. Resistance has been associated with defective expression of functional SS (SSTR2–5) and DA (DRD2) receptors. The role of cytoskeleton proteins in receptor trafficking, anchoring to the plasma membrane and signalling has been demonstrated in other tumoral cell systems. In particular, filamin A (FLNA) seems to be a good candidate. In fact, it is implicated in the regulation of DRD2 localization and signalling in different cell types. In particular, we recently demonstrated that both FLNA and DRD2 are strongly reduced or absent in DA-resistant prolactinomas. Moreover, FLNA overexpression in primary cultured cells from resistant prolactinomas restores D2R expression and PRL responsiveness to DA. On the contrary, in cultured cells from DA-sensitive prolactinomas and MMQ cells FLNA silencing resulted in a reduction of D2R expression and abrogation of DA-induced inhibition of PRL release and antiproliferative signals. These data indicate that FLNA is crucial for D2R expression and signaling in lactotrophs, suggesting that the impaired response to DA may be related to the reduction of FLNA expression in DA-resistant prolactinomas.

Since SSTR2 was recently found to associate with FLNA, we investigated a possible role of FLNA in regulating SSTR2 targeting and signaling in GH-secreting adenomas. To this purpose, we performed FLNA silencing in GH-secreting adenoma cultured cells. Preliminary data showed that FLNA silencing did not affect neither SSTR2 localization at the plasma membrane nor its expression stability. On the contrary, the reduction in cyclin D1 levels induced by the selective SSTR2 agonist was abolished in FLNA silenced cells, suggesting that FLNA might be implicated in intracellular signalling of SSTR2 by mediating its antiproliferative effects without affecting receptor expression and localization at the plasma membrane.

Article tools

My recent searches

No recent searches.