{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:14:55Z","timestamp":1791288895574,"version":"4.3.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> The molecular mechanisms responsible for glucose\u2010dependent insulinotrophic peptide receptor or gastric inhibitory polypeptide receptor (GIPR) ectopic expression and function in GIP\u2010dependent Cushing's syndrome (CS) are still unknown. GIPR presumably acts, like the ACTH receptor (ACTHR), through the Gs protein\/cyclic AMP\/protein kinase\u00a0A (PKA) pathway to stimulate steroidogenesis. We studied the expression of several genes involved in this pathway in the adrenal tissues of patients with GIP\u2010dependent CS.<\/jats:p><jats:p><jats:bold>Design and methods\u2002<\/jats:bold> RNA was extracted from adrenal tissues from nine patients with GIP\u2010dependent CS [seven ACTH\u2010independent bilateral macronodular adrenal hyperplasia (AIMAH), two adenomas], two control whole adult adrenals, two fasciculata cell\u2010enriched preparations from normal adrenals, seven patients with Cushing's disease (CD) and two normal pancreas. Multiplex reverse transcriptase polymerase chain reaction (RT\u2010PCR) evaluated the expression of GIPR, ACTHR, SF\u20101, Nur77, DAX\u20101, CYP11A, 3\u03b2\u2010HSD, CYP21, CREB and CREM genes.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> GIPR mRNA was overexpressed in all GIP\u2010dependent cases. In normal adrenals and in the adrenal tissues from patients with CD, minimal amounts of GIPR mRNA were detected. ACTHR mRNA expression was observed in all GIP\u2010dependent adrenal tissues. The expression of steroidogenic enzymes and some specific and ubiquitous transcription factors (TFs) involved in the ACTHR cascade was significantly reduced.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Our results indicate that the expression of ACTHR and other genes located downstream in the ACTHR cascade, including steroidogenic enzymes genes and some transcription factors, are relatively suppressed in GIP\u2010dependent CS. Although the expression of aberrant receptors plays an important role in steroidogenesis and initiation of cell proliferation, additional genetic events might occur, altering the activity of the ACTHR pathway.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2005.02411.x","type":"journal-article","created":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T18:08:54Z","timestamp":1133460534000},"page":"29-36","source":"Crossref","is-referenced-by-count":38,"title":["Expression of ACTH receptor pathway genes in glucose\u2010dependent insulinotrophic peptide (GIP)\u2010dependent Cushing's syndrome"],"prefix":"10.1111","volume":"64","author":[{"given":"Sonir R.","family":"Antonini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Baldacchino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Hamet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Lacroix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.10.3531"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.22.1.75"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.5.1980"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(04)00188-2"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.8.2781"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2004.03.120"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.12.4514"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.9.3134"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117168"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90160-0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.42.475"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1997.1991009.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2000.00932.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04339.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1340583"},{"key":"e_1_2_6_17_2","first-page":"215","article-title":"ACTH\u2010independent macronodular adrenocortical hyperplasia: immunohistochemical and in situ hybridization studies of steroidogenic enzymes","volume":"7","author":"Sasano H.","year":"1994","journal-title":"Modern Pathology"},{"key":"e_1_2_6_18_2","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2144\/99275rr04","article-title":"Multiplex relative RT\u2010PCR method for verification of differential gene expression","volume":"27","author":"Spencer W.E.","year":"1999","journal-title":"Biotechniques"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0020169"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1211395"},{"key":"e_1_2_6_21_2","doi-asserted-by":"crossref","unstructured":"Swords F.M. 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