Receptor-mediated internalization is critical for the inhibition of the expression of growth hormone by somatostatin in the pituitary cell line AtT-20.
The inhibitory effect of the neuropeptide somatostatin on the expression of growth hormone was measured by quantitative polymerase chain reaction in the pituitary cell line AtT-20. We demonstrate that this effect is dependent on the internalization of somatostatin-receptor complexes and that it is totally independent from the peptide-induced inhibition of adenylate cyclase. Indeed, the inhibitory effect of the peptide on growth hormone mRNA levels was totally insensitive to pertussis toxin treatment but was totally abolished under conditions which block somatostatin receptor internalization. Comparative confocal microscopic imaging of fluorescent somatostatin sequestration and fluorescence immunolabeling of sst1, sst2A, and sst5 receptors suggests that sst2A is most probably responsible of the inhibitory effect of somatostatin on growth hormone expression.
Sarret
P
P
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UPR 411, 660 Route des Lucioles, 06560 Valbonne, France.
Nouel
D
D
Dal Farra
C
C
Vincent
J P
JP
Beaudet
A
A
Mazella
J
J
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D013006:Growth Hormone / Q000096:biosynthesis*; D008024:Ligands; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008024:Ligands; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013004:Somatostatin; D013006:Growth Hormone; D000242:Cyclic AMP