Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm

Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, oth er steroid-producing organs are sites of inhibin alpha subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel o f 150 adrenals (10 normal adrenals, 25 adrenocortical hyperplasias, 65 adre nocortical adenomas, 30 adrenocortical carcinomas and 20 phaeochromocytomas ) for inhibin alpha expression, mRNA levels of inhibin alpha subunit were s tudied in 57 samples and all tissues were stained immunohistochemically wit h an inhibin alpha subunit-specific antibody. Inhibin ct mRNA was detected in all adrenocortical tissues. Virilizing adenomas possessed a 10-fold high er median inhibin alpha mRNA expression than did normal adrenals. Bilateral ly and nodularly hyperplastic adrenals and other than virilizing adrenocort ical rumours had their median inhibin a mRNA levels close to those of norma l adrenals. Imnlunohistochemically, inhibin alpha subunit was detectable in all normal and hyperplastic adrenals, as well as in 73% of the adrenocorti cal tumours. However, the percentage of inhibin alpha-positive cells varied greatly in different tumour types. The median percentage of positive cells was 10 in non-functional and Conn's adenomas, 30 in Gushing's adenomas and 75 in virilizing adenomas. In malignant adrenocortical rumours the median percentage of inhibin alpha-immunopositive cells was 20 in non-functional c arcinomas, 30 in Conn's carcinomas, 65 in Gushing's carcinomas and 75 in vi rilizing carcinomas. All phaeochromocytomas were negative for inhibin alpha subunit both at the mRNA level and immunohistochemically. Our data show that inhibin alpha subunit is highly expressed in both normal and neoplastic androgen-producing adrenocortical cells, with less expressi on in cortisol-producing and hardly any in aldosterone-producing cells. Thi s suggests a specific role for inhibins in the regulation of adrenal androg en production. We did not find any significant difference in inhibin alpha expression between benign and malignant adrenocortical tumours. Thus inhibi n alpha gene does not seem to have a tumour suppressor role in human adrena l cortex.