Expression of adrenocorticotrophic hormone receptor mRNA in human adrenocortical neoplasms: correlation with P450scc expression.
OBJECTIVE
Adrenocorticotrophin (ACTH) is the main hormone-regulating steroid secretion from the adrenal cortex. The ACTH receptor (ACTH-R) has recently been cloned, allowing systematic evaluation of its expression and function in adrenal tumorigenesis. We investigated ACTH-R and P450 side-chain cleavage enzyme (P450scc) mRNA expression in a variety of neoplastic adrenocortical tissues by Northern blot and reverse-transcriptase-PCR (RT-PCR).


METHODS
We studied tissue from eight normal adrenals, six diffuse adrenocortical hyperplasias in patients with ACTH-dependent Cushing's syndrome, 22 adrenal adenomas, six carcinomas and two carcinoma cell lines. Poly A mRNA was electrophoresed, immobilized on a nylon membrane and hybridized using alpha 32P-CTP labelled human ACTH-R and P450scc cDNAs.


RESULTS
Mean ACTH-R mRNA expression showed significant differences between groups (P = 0.0001), but appeared to be independent of plasma ACTH concentrations. Compared to normal adrenal (= 100 +/- 12%), expression was low in non-functional adenomas (23 +/- 11%) and carcinomas (19 +/- 12%), intermediate in adrenocortical hyperplasias (88 +/- 6%) and cortisol-producing adenomas (81 +/- 15%) and high in aldosteronomas (175 +/- 29%). In adenomas, ACTH-R mRNA expression correlated closely with the expression of P450scc mRNA(r = 0.8, P = 0.0001) suggesting regulation by similar factors. However, carcinomas and cancer cell lines did not show a positive correlation between these two parameters (r = -0.44, P = 0.3).


CONCLUSIONS
We have demonstrated that plasma ACTH is not the major factor influencing ACTH-receptor mRNA expression in neoplastic adrenal tissue. In benign tumours of the adrenal cortex there was a close positive correlation between ACTH-receptor mRNA and P450scc mRNA which was missing in adrenocortical carcinomas, probably as a result of tumour dedifferentiation.
Reincke
M
M
Department of Internal Medicine, University of Würzburg, FRG.
Beuschlein
F
F
Latronico
A C
AC
Arlt
W
W
Chrousos
G P
GP
Allolio
B
B
D000236:Adenoma / Q000737:chemistry*; D000302:Adrenal Cortex / Q000737:chemistry / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000737:chemistry*; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D002277:Carcinoma / Q000737:chemistry*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D018043:Receptors, Corticotropin / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000737:chemistry
D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D002786:Cholesterol Side-Chain Cleavage Enzyme