Glucocorticoid negative feedback in sheep corticotrophs: a comparison with AtT-20 corticotroph tumor cells.
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.
Clark
T P
TP
Department of Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama 36849.
Kemppainen
R J
RJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005246:Feedback; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012016:Reference Values; D012756:Sheep; D013268:Stimulation, Chemical; D013997:Time Factors; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D009543:Nifedipine