Northern blot analysis revealed that the size of pro-opiomelanocortin mRNA present in the SCCA tissue was indistinguishable from that in the adenomas associated with Cushing's disease.
These results indicate that subtype 1 silent adenomas and clinically active adenomas associated with Cushing's disease contain POMC mRNA that is readily detectable by ISH in routinely processed tissue specimens, while only a few of the subtypes 2 and 3 adenomas have POMC mRNA that can be detected in paraffin blocks with the oligonucleotide probes used in this study.
No PC2 messenger ribonucleic acid could be detected in the small cell carcinoma of the lung-derived DMS-79 human cell line, which produces unprocessed POMC, or in three pituitary tumors responsible for Cushing's disease or Nelson's syndrome, which produced intact ACTH, but no CLIP.
We speculate that the response to the desmopressin test observed in patients with Cushing's disease may be due to abnormal expression of V3R or V2R in ACTH-secreting tumors.
Nelson's syndrome is the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for Cushing's disease.
This case illustrates that ACTH stimulation by desmopressin is not specific for pituitary-dependent Cushing's syndrome as vasopressin receptor subtypes known to interact with desmopressin may also be found in ectopic tumours producing ACTH.
In conclusion, the DDAVP stimulation test, i.e., determination of plasma ACTH levels after 5 microg DDAVP injection, seems useful for discriminating Cushing's disease from normality, and may serve to facilitate the differentiation between Cushing's disease and ectopic ACTH syndrome.
Recently it was shown that patients with pituitary corticotrope adenomas respond to GHS with a dramatic rise in ACTH secretion, and it has been suggested that GHS may provide a diagnostic tool to differentiate Cushing's disease from the ectopic ACTH syndrome.
We have hypothesized that abnormalities of the glucocorticoid receptor (GR) gene might play a role in the development of Cushing's disease via an increase in the relative production of the nonligand-binding splice variant of the GR, GR beta, known to exert dominant negative effects over the ligand-binding isoform, GR alpha.
We screened for the GR gene in leukocyte and tumor DNA from 22 patients with Cushing's disease for mutations using PCR/single strand conformation polymorphism analysis.
These results suggest strongly that decreased expression of GR alpha in pituitary adenomas may be the major reason for the marked insensitivity to the 8-mg dexamethasone suppression test observed in two patients with Cushing's disease.
Hypertension is a prominent feature of patients with Cushing's disease and ectopic adrenocorticotropic hormone (ACTH) syndrome, who have elevated ACTH levels.
In conclusion the down-regulation of Bcl-2 in Cushing's disease did not agree with no induction of this gene by cAMP in H295R cells, suggesting that expression of Bcl-2 protein was not regulated mainly by cAMP-protein kinase (PKA) pathways in human adrenal hyperplasia.