ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2010) 22 OC3.1 
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Sgk1 effects on POMC transcription and ACTH release are opposite to those of glucocorticoids

Marie Helene Reiter1, Greisa Vila1, Sabina M Baumgartner-Parzer1, Engelbert Knosp2, Ludwig Wagner1, Günter K Stalla3 & Anton Luger1

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Glucocorticoid feed-back in pituitary corticotrophs represses POMC transcription and ACTH release. Serum and glucocorticoid-induced kinase 1 (Sgk1) has been identified as an immediate early target of glucocorticoids in many tissues, however its expression and function in corticotrophs are unknown.

We show here that Sgk1 is present in the human pituitary gland at both mRNA and protein levels. Double-immunohistochemistry revealed that Sgk1 is expressed in different cell types and, among others, co-localises with ACTH. The AtT-20 corticotroph cell line was used for functional experiments. Dexamethasone at 100 nM increases Sgk1 transcription within 30 min as identified by real time PCR. Twenty-four hours after dexamethasone, Sgk1 protein levels increase in all cellular subfractions in western blotting. This effect is abolished by RU486, confirming the mediation of dexamethasone response by the glucocorticoid receptor. The increase in phosphorylated Sgk1 is reduced by co-stimulation with LY294002, pointing towards post-translational activation via a PI3K-dependent pathway. Independently of glucocorticoids, Sgk1 overexpression increases CREB- and AP-1-dependent transcription, c-jun phosphorylation, POMC luciferase reporter values and ACTH secretion. Within one experiment, Sgk1 overexpression increases POMC promoter activity similarly to CRH. Nevertheless, there is an additive effect of both stimulants on POMC transcription, implying the existence of additional signalling pathways downstream of Sgk1. Sgk1 knockdown via siRNA decreases POMC promoter activity without significantly changing ACTH release.

In summary, Sgk1 is strongly stimulated by glucocorticoids in pituitary corticotrophs; however its effects on POMC transcription are antagonistic to the classical glucocorticoid-mediated inhibition, suggesting Sgk1 may protect cells from possibly detrimental glucocorticoid action.

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