Endocrinology, Vol 126, 809-817, Copyright © 1990 by Endocrine Society

ARTICLES

Effect of secretagogues on components of the secretory system in AtT-20 cells

EA Thiele and BA Eipper
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

The mouse corticotrope tumor cell line AtT-20/D16v was used to investigate the effects of chronic treatment with various secretagogues on individual components of the secretory pathway. Secretagogues acting in part through receptors linked to guanine nucleotide-binding regulatory proteins [CRF and somatostatin (SS)] and agents by-passing membrane receptors (phorbol myristate acetate and dexamethasone) were examined. Effects on the secretory product were evaluated by measuring levels of pro-ACTH/endorphin mRNA and hormone secretion. Effects on posttranslational processing enzymes were evaluated by measuring levels of the mRNAs encoding carboxypeptidase-E and peptidyl-glycine-alpha- amidating monooxygenase (PAM); cellular levels of PAM activity were also measured. The mRNAs encoding the G-proteins in AtT-20 cells were identified, and secretagogue effects on the G-protein signal transduction system were evaluated by measuring levels of the mRNAs encoding (alpha s, alpha)i2, and beta 2. No single parameter adequately characterizes the regulatory state of the complex secretory apparatus. Although levels of pro-ACTH/endorphin (PAE) mRNA accurately reflected hormone secretion after chronic CRF or dexamethasone treatment, chronic SS treatment elevated PAE mRNA levels in the face of reduced hormone secretion. Levels of PAM mRNA generally changed in parallel with levels of PAE mRNA; in contrast, levels of carboxypeptidase-E mRNA were unaffected by any of the secretagogues tested. Secretagogues acting through distinct G-proteins (CRF and SS) as well as dexamethasone brought about a coordinate increase in the level of the mRNAs encoding the three G-protein subunits examined. Treatment with phorbol myristate acetate caused a slight decrease in the levels of the G-protein subunit mRNAs.

This article has been cited by other articles:

				A. M. Oyarce and B. A. Eipper Cell Type-specific Storage of Dopamine beta -Monooxygenase J. Biol. Chem., February 4, 2000; 275(5): 3270 - 3278. [Abstract] [Full Text] [PDF]

				G. D. Ciccotosto, M. R. Schiller, B. A. Eipper, and R. E. Mains Induction of Integral Membrane PAM Expression in AtT-20 Cells Alters the Storage and Trafficking of POMC and PC1 J. Cell Biol., February 8, 1999; 144(3): 459 - 471. [Abstract] [Full Text] [PDF]

				T. O. Bruhn, J. M. M. Rondeel, and I. M. D. Jackson Thyrotropin-Releasing Hormone Gene Expression in the Anterior Pituitary. IV. Evidence for Paracrine and Autocrine Regulation Endocrinology, August 1, 1998; 139(8): 3416 - 3422. [Abstract] [Full Text] [PDF]