The effect of selective sst1, sst2, sst5 somatostatin receptors agonists, a somatostatin/dopamine (SST/DA) chimera and bromocriptine on the "clinically non-functioning" pituitary adenomas in vitro.
The aim of the work was to investigate the effects of somatostatin analogs acting selectively on sst1 (BIM-23926), sst2 (BIM-23120) and sst5 (BIM-23206) receptor subtypes on the viability of "clinically non-functioning" pituitary adenomas in vitro. The effects of native SST (SST-14), a SST/DA chimera (BIM-23A387) and a D(2)-dopamine receptor agonist bromocriptine (BC) were also examined. The study was performed on 10 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". A part of each tumor was mechanically dispersed and digested with collagenase to isolate the tumoral cells. Another part of each tumor was fixed, embedded in paraffin and immunostained to reveal the pituitary hormones and SST receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, sst5). The tumoral cell suspensions were incubated for 24 h with the substances mentioned above. The quantity of viable cells was estimated using the EZ4U system. The results were compared with the immunohistochemical evaluation of the hormonal profile of adenoma and the sst receptor subtype immunoreactivities present. The findings indicate that selective sst1, sst2 and sst5 receptors agonists, SST/DA chimera and D(2)-dopamine receptor agonist bromocriptine affect the viability of some, but not all, "clinically non-functioning" pituitary adenomas in vitro. The most effective was bromocriptine. The investigated somatostatin analogs including SST/DA chimera exerted roughly similar inhibitory effects. Further studies are needed to fully evaluate the potential usefulness of these compounds in the pharmacological treatment of "non-functioning" pituitary tumors.
Gruszka
A
A
Chair of Endocrinology, Medical University of Lodz, Poland.
Kunert-Radek
J
J
Radek
A
A
Pisarek
H
H
Taylor
J
J
Dong
J Z
JZ
Culler
M D
MD
Pawlikowski
M
M
D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001971:Bromocriptine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011954:Receptors, Dopamine / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D014408:Biomarkers, Tumor; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; C101130:somatostatin receptor type 1; D001971:Bromocriptine; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2