Dissociation of early glucocorticoid inhibition of ACTH secretion and glucose uptake in mouse AtT20 D16:16 corticotrophs.
Adrenal glucocorticoid hormones rapidly exert powerful effects on neurons, immune and neuroendocrine cells through induction of de novo protein synthesis. In this study, we investigated, using mouse clonal anterior pituitary AtT20 D16:16 corticotrophs, whether (i) glucocorticoids rapidly inhibit glucose transport and (ii) whether this inhibition of glucose transport is directly correlated with early inhibition of ACTH secretion. Glucose uptake in AtT20 D16:16 cells was Na+-independent because the Na+-independent glucose transport inhibitor phloretin (100 microM) completely inhibited specific 14C-deoxygluose (DoG) uptake and replacement of extracellular Na+ with N-methyl D-glucamine+ had no effect. Furthermore, the Na+-independent glucose transporters, GLUTs 1 and 3 were expressed in AtT20 D16:16 cells. The synthetic type II glucocorticoid receptor agonist dexamethasone, rapidly, within 2 h, inhibited DoG uptake into AtT20 D16:16 cells through a mechanism that was dependent on de novo mRNA synthesis. Glucocorticoid inhibition of glucose transport was not correlated with early inhibition of ACTH secretion because removal of glucose from the external medium had no effect on CRF-stimulated ACTH secretion or the efficacy of early glucocorticoid inhibition of ACTH release. Although the Na+-independent glucose transport inhibitor phloretin significantly inhibited CRF-stimulated ACTH release, this effect of phloretin was a result of its potent activation of large conductance calcium-activated potassium (BK) channels. These data suggest that different molecular pathways and/or glucocorticoid induced proteins underlie the mechanism(s) of early glucocorticoid inhibition of glucose uptake and ACTH release, respectively.
Department of Physiology, The Medical School, University of Edinburgh, UK.
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C
Booth
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Tian
M J
MJ
Shipston
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D010693:Phloretin / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D005947:Glucose; D010693:Phloretin