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J Biol Chem, Vol. 274, Issue 27, 19294-19300, July 2, 1999

Receptor-mediated Internalization Is Critical for the Inhibition of the Expression of Growth Hormone by Somatostatin in the Pituitary Cell Line AtT-20

Philippe Sarret, Dominique Nouel^§, Claude Dal Farra, Jean-Pierre Vincent, Alain Beaudet^§, and Jean Mazella

From the  Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UPR 411, 660 Route des Lucioles, 06560 Valbonne, France and the ^§ Montreal Neurological Institute, McGill University, Montréal, Québec H3A 2B4, Canada

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.

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