AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 2 463-R469, Copyright © 1994 by American Physiological Society
Glucocorticoid negative feedback in sheep corticotrophs: a comparison with AtT-20 corticotroph tumor cells
T. P. Clark and R. J. Kemppainen
Department of Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama 36849.
Early glucocorticoid feedback in sheep anterior pituitary (AP) cells was
compared and contrasted with that in mouse pituitary tumor AtT-20 cells.
Dexamethasone (DEX) inhibited corticotropin-releasing hormone
(CRH)-stimulated adrenocorticotropin (ACTH) release in a concentration- and
time-dependent manner with similar potency amongst cell types. This
inhibition was mediated through type II glucocorticoid receptors and
required the synthesis of new protein. However, stimulation of protein
kinase C with phorbol 12-myristate 13-acetate (PMA) resulted in greater
ACTH release and greater inhibition by DEX in sheep AP cells. In contrast
to sheep AP cells, AtT-20 cells were insensitive to glucocorticoids when
secretion was stimulated by KCl depolarization or the voltage-dependent
calcium channel agonist, maitotoxin (MTX). In both cell types, CRH-, KCl-,
and MTX-stimulated ACTH release was inhibited by the calcium channel
blocker, nifedipine (NIF). Whereas NIF also inhibited PMA-induced ACTH
secretion in AtT-20 cells, it did not in sheep AP cells. These data
demonstrate that early glucocorticoid feedback is operative in sheep
corticotrophs and that AtT-20 cells appear to serve as an appropriate
mechanistic model for aspects of negative feedback when the CRH-protein
kinase A pathway is activated but may not be appropriate when ACTH
secretion is activated via other intracellular signaling pathways.
