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We have recently demonstrated the activation of CRTC isoforms, CRTC1 and CRTC3, in adrenocortical cell lines. In the present study, we aimed to determine the activation and expression of the three CRTC isoforms in vivo in relation to <jats:italic>Star<\/jats:italic> transcription, under basal conditions and following a robust endotoxic stress challenge. Rat adrenal glands and blood plasma were collected following i.v. administration of either an ultradian\u2010sized pulse of ACTH or administration of lipopolysaccharide, as well as under unstressed conditions across the 24\u2010hour period. Plasma ACTH and corticosterone (CORT) were measured and the adrenal glands were processed for measurement of protein by western immunoblotting, RNA by a quantitative reverse transcriptase\u2010polymerase chain reaction and association of CRTC2 and CRTC3 with the <jats:italic>Star<\/jats:italic> promoter by chromatin immunoprecipitation. An increase in nuclear localisation of CRTC2 and CRTC3 followed increases in both ultradian and endotoxic stress\u2010induced plasma ACTH, and this was associated with increased CREB phosphorylation and corresponding increases in <jats:italic>Star<\/jats:italic> transcription. Both CRTC2 and CRTC3 were shown to associate with the <jats:italic>Star<\/jats:italic> promoter, with the dynamics of CRTC3 binding corresponding to that of nuclear changes in protein levels. CRTC isoforms show little variation in ultradian expression or variation across 24\u00a0hours, although evidence of long\u2010term down\u2010regulation following endotoxic stress was found. We conclude that co\u2010transcription factors CRTC2 and, more clearly, CRTC3 appear to act alongside phosphorylated CREB in the generation of ultradian pulses of <jats:italic>Star<\/jats:italic> transcription, essential for the maintenance of basal StAR expression. Similarly, our findings suggest CRTC2 and CRTC3 mediate <jats:italic>Star<\/jats:italic> transcriptional initiation following an endotoxic stressor; however, other transcription factors are likely to be responsible for the long\u2010term up\u2010regulation of adrenal <jats:italic>Star<\/jats:italic> transcription.<\/jats:p>","DOI":"10.1111\/jne.12920","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T12:09:37Z","timestamp":1605701377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Activation and expression of endogenous CREB\u2010regulated transcription coactivators (CRTC) 1, 2 and 3 in the rat adrenal gland"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-9192","authenticated-orcid":false,"given":"Lorna I. 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