Expression of activin and inhibin subunits, receptors and binding proteins in human adrenocortical neoplasms.
OBJECTIVE
The growth and differentiation factors activin and inhibin can affect tumour formation and steroid production in the adrenal cortex. These factors bind to type I (Alk-4), type II (ActRIIA, ActRIIB) and type III (betaglycan) receptors or to the activin-binding protein follistatin. Expression of these activin-related mRNAs was measured in different types of adrenocortical tissues and tumours to study the relationship with tumorigenesis.


METHODS
Quantitative expression of activin-related mRNAs was investigated in patient adrenocortical samples.


METHODS
Twenty-eight human adrenocortical samples from normal and hyperplastic adrenals and from adrenocortical adenomas and carcinomas were collected after surgery for study purposes.


METHODS
Using quantitative reverse transcription polymerase chain reaction (RT-PCR), we investigated the expression of inhibin alpha-, betaA- and betaB-subunits, follistatin, betaglycan, ActRIIA, ActRIIB and Alk-4 in the adrenocortical tissues. The expression of cytochrome P450c17 (CYP17) mRNA was also measured to investigate its association with inhibin and activin subunit expression.


RESULTS
All genes studied were expressed in all tissues, with the exception of the inhibin alpha-subunit in one hyperplastic adrenal and three adrenocortical carcinomas. Expression of inhibin betaA-subunit, follistatin, betaglycan, ActRIIA, ActRIIB and CYP17 differed between nontumorous adrenals and carcinomas.


CONCLUSIONS
These differences, together with correlation analysis, indicate parallel regulation of the expression of CYP17, the inhibin alpha-subunit, ActRIIA, ActRIIB, betaglycan and follistatin. We conclude that the expression of activin and inhibin subunits, receptors and binding proteins is affected by tumour formation in the adrenal gland and may play a role in tumorigenesis.
Hofland
J
J
Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Rotterdam, the Netherlands.
Timmerman
M A
MA
de Herder
W W
WW
van Schaik
R H N
RH
de Krijger
R R
RR
de Jong
F H
FH
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D018246:Adrenocortical Adenoma / Q000378:metabolism*; D018268:Adrenocortical Carcinoma / Q000378:metabolism*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D038681:Follistatin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D038681:Follistatin; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C103008:inhibin beta A subunit; C094377:inhibin-alpha subunit; D028341:Activins; C071736:betaglycan; D007265:Inhibins; D028322:Inhibin-beta Subunits; D013254:Steroid 17-alpha-Hydroxylase; D030301:Activin Receptors, Type II