This Article Full Text Full Text (PDF) All Versions of this Article: 90/11/6237    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hagendorf, A. Articles by Feelders, R. A. Search for Related Content PubMed PubMed Citation Articles by Hagendorf, A. Articles by Feelders, R. A. Related Collections Adrenal and Hypertension

Expression of the Human Glucocorticoid Receptor Splice Variants , ß, and P in Peripheral Blood Mononuclear Leukocytes in Healthy Controls and in Patients with Hyper- and Hypocortisolism

Department of Internal Medicine, Section of Endocrinology (A.H., J.W.K., F.H.d.J., S.W.J.L., R.A.F.), and Department of Reproduction and Development (A.O.B.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Jan W. Koper, Department of Internal Medicine, Section of Endocrinology, Room Ee 585, Erasmus Medical Center, P.O.B. 2040, 3000 CA Rotterdam, The Netherlands. E-mail: f.koper{at}erasmusmc.nl.

Context: The effects of cortisol are mediated by the -isoform of the glucocorticoid receptor (GR). GR- levels and activity are modulated by alternative splicing of the common pre-mRNA into mRNAs for the GR-ß and GR-P isoforms.

Objective: The objective of this study was to investigate whether chronic hypercortisolism, chronic hypocortisolism, or acute, relative hypocortisolism influences the expression levels of the GR splice variants in mononuclear leukocytes.

Design: This was a case-control study.

Setting: The study was performed at a university hospital.

Participants: Eighteen patients with Cushing’s syndrome, five patients with hypocortisolemia, seven patients undergoing metyrapone testing, and 14 controls were studied.

Main Outcome Measures: The main outcome measures were mRNA levels, GR affinity, and number per cell.

Results: All three GR mRNA isoforms were detected in participants from all groups at relative levels of /P/ß = 1:0.25:0.001. There was a significant correlation between the expression levels of the three splice variants and between the mRNA levels and the number of receptors per cell. The GR in Cushing patients had an increased K_d (P < 0.05) preoperatively. GR number was not significantly different. Postoperatively, the K_d decreased. GR-ß mRNA expression was increased compared with controls (P < 0.05) and was decreased after surgery (P < 0.05). In patients with chronic hypocortisolism, GR- mRNA expression was increased, and receptor numbers were increased (P < 0.05), whereas GR affinity was normal. No changes were observed in patients undergoing a metyrapone test.

Conclusions: Cushing’s syndrome is accompanied by a reversible decrease in GR affinity, possibly related to an increased GR-ß expression, which may be a compensatory mechanism to GC excess. In chronic hypocortisolism, adaptive changes in GR status seem to occur at the level of GR number.

This article has been cited by other articles:

				J. L. Chisa and D. T. Burke Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled Genetics, March 1, 2007; 175(3): 1079 - 1087. [Abstract] [Full Text] [PDF]

				H. Russcher, V. A S H Dalm, F. H de Jong, A. O Brinkmann, L. J Hofland, S. W J Lamberts, and J. W Koper Associations between promoter usage and alternative splicing of the glucocorticoid receptor gene J. Mol. Endocrinol., January 1, 2007; 38(1): 91 - 98. [Abstract] [Full Text] [PDF]