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. Design: Quantitative expression of activin-related mRNAs was investigated in patient adrenocortical samples. Patients: Twenty-eight human adrenocortical samples from normal and hyperplastic adrenals and from adrenocortical adenomas and carcinomas were collected after surgery for study purposes. Measurements: Using quantitative reverse transcription polymerase chain reaction (RT-PCR), we investigated the expression of inhibin α-, βA- and βB-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 α-subunit in one hyperplastic adrenal and three adrenocortical carcinomas. Expression of inhibin βA-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 α-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.