Expression of a nuclear transcription factor "Ad4BP" , a common factor to regulate steroidogenic cytochrome P450, in adrenal tumor

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Adrenocortical tumors can be divided in two categories, functioning and non-functioning. The patients with functioning ademona manifest clinical symptoms such as Cushing's syndrome or Conn's syndrome. Recently it has been shown that the expression of steroidogenic enzymes is under the control of several transcription factors such as Ad4-BP,NGFI-B and COUP-TF.However there is few report how these transcription factors are regulated in the adrenal glands. Also no known is the expression of these factors in adrenocortical tumors. It is thus studied whether adrenocorticotropin (ACTH) regulates the expression of Ad4-BP,NGFI-B and COUP-TFin rats. Also studied was the expression of these factors in human adrenocortical tumors obtained at surgery.In the experiment using rat, dexamethsone was administered to completely suppress ACTH secretion. The animals were then treated with ACTH and the adrenal glands were obtained at intervals. Northern blot analysis revealed that the expression of NGFI-B … More and COUP-TF mRNA was at undetectable level before ACTH aministration. NGF-IB mRNA was rapidly induced by ACTH (detectable at 30 min and a peak at 60 min after ACTH). The mRNA became undetectable at 180 min after ACTH.Induction of COUP-TF was somewhat lagged after NGF-IB but the increased level was maintained even 180 min after ACTH.These results indicate that NGF-IB and COUP-TF mediate ACTH action through induction of their mRNAs. When ACTH-receptor mRNA level was studied, it was clearly demonstrated that ACTH increases its own receptor mRNA.The result indicates that ACTH is required for the expression of its mRNA.The study with human adrenocortical samples revealed that Ad4BP mRNA isalways detectable in the adenoma obtained from the patients with Cushing's syndrome as well as primary aldosterone producing adenoma. When ACTH-receptor mRNA was analyzed in two adrenal samples from the patients with Cushing's syndrome, it was noted that adenoma contained abundant ACTH-receptor mRNA.However, the abundance of the mRNA was extremely low in the adjacent normal adrenal tissues. The suppressed ACTH-receptor mRNA in the normal tissue is compatible with the finding from the experiments with rats that ACTH is required for the expression of its mRNA.The expression of ACTH-receptor mRNA in the adenoma tissue was surprizing. It suggest that regulation of ACTH-receptor mRNA is altered in the adenoma tissue. Less