Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.579082
Title: Regulation of the transcription factor nuclear factor kappa B in the neuroendocrine response to stress
Author: Mehet, Devinder Kaur
ISNI:       0000 0004 2743 3674
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2007
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Abstract Lipopolysaccharide (LPS) activates the hypothalamo-pituitary adrenal (HPA) axis, possibly by acting on the anterior pituitary gland. Whilst the mechanisms governing this response are unclear, LPS induces many of its effects via the glucocorticoid sensitive pro-inflammatory transcription factor, nuclear factor kappa B (NFKB). The present study tested the hypothesis that LPS promotes adrenocorticotrophin (ACTH) release via an NFKB-dependent mechanism and may be a target for the negative feedback actions of glucocorticoids. Two murine pituitary cell lines, which were found to express an intact LPS signalling system, were utilised alone and in co-culture to model folliculostellate (TtT/GF cells) and corticotroph (AtT20 D16:16 cells) inter-communication. TtT/GF cell-derived interleukin 6 (IL-6) release was induced by LPS via an NR(B-dependent mechanism and inhibited by dexamethasone. Although LPS did not directly affect basal ACTH secretion from the AtT20 D16:16 cells, recombinant IL-6 potentiated the stimulatory effect of CRH, supporting the premise that LPS increases ACTH release via actions of folliculostellate cell-derived IL-6. In contrast, LPS-induced NFKB activity in the AtT20 D16:16 cells inhibited CRH-induced ACTH release. In the co-culture studies, CRH increased ACTH secretion directly and indirectly by stimulating IL-6 release from the TtT/GF cells, possibly via actions of AtT20 D16:16 cell-derived mediator(s). These findings support the hypothesis that NFKB signalling in folliculostellate cells promotes ACTH secretion and is sensitive to the inhibitory effects of glucocorticoids, whilst corticotroph NFKB signalling inhibits CRH-induced ACTH secretion.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.579082  DOI: Not available
Share: