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EXPRESSION OF INHIBIN & IN THE HUMAN ADRENAL GLAND AND ADRENOCORTICAL TUMORS
J. Arola, J. Liu, P. Heikkilä, R. Voutilainen and A. Kahri
Haartman Institute, Department of Pathology, P.O.Box 21, FIN-00014, University of Helsinki, Finland
ABSTRACT
We studied the expression of inhibin a-subunit in normal and hyperplastic adrenal glands, as well as in various adrenocortical tumors. The protein expression of inhibin a was performed by immunohistochemistry. Virilizing adenomas showed strong immunoreactivity against monoclonal inhibin «-subunit antibody, whereas other adenomas were only weakly positive or completely negative. In the adrenal cortex no inhibin & immunoreactivity was detected in the zona glomerulosa. Zona fasciculata showed weak staining for inhibin a, however, strong immunostaining was detected in zona reticularis both in normal and hyperplastic adrenal glands. Adrenal medulla was negative for inhibin a. In conclusion, we show high expression of inhibin & subunit in zona reticularis of normal and hyperplastic adrenal glands as well as strong expression in virilizing adenomas.
INTRODUCTION
Inhibin a is a common subunit of two heterodimeric glycoproteins linked to either a BA-(inhibin A) or BB-subunit (inhibin B). Steroid-producing organs are the main sites of inhibin a-subunit expression (1). The role of adrenal inhibins is not fully understood. Although, gonads are the main source of circulating inhibins, adrenal veins have a higher concentration of inhibins compared to peripheral blood suggesting some contribution of adrenals as well (2). Inhibins have also been suggested to be tumor suppressors for the adrenal gland, since gonadectomized inhibin-deficient mice develop adrenocortical tumors.
Two recent papers reported immunoreactivity against inhibin & in adrenocortical tumors (4,5). To further analyze the role of adrenal inhibins, we studied the expression of inhibin a-subunit in normal and hyperplastic human adrenal glands, as well as in various adrenocortical tumors.
MATERIALS AND METHODS
Tissue material was obtained during operations performed at the Department of Surgery, Helsinki University Central Hospital. Normal adrenal glands were obtained from 10 patients who underwent nephrectomy for renal carcinoma. Pathological adrenal tissues included 3 Conn’s adenomas, 3 Cushing’s adenomas and 3 virilizing adenomas, as well as 2 bilateral hyperplasias and hormonally active (3) or inactive (3) adrenocortical carcinomas. Immunohistochemistry was performed with a monoclonal antibody against Inhibin A ( Serotec Ltd., Oxford, U.K.).
RESULTS
Normal adrenal cortex possessed strong immunoreactivity against inhibin & in zona reticularis. Weak reactivity was seen in zona fasciculata, whereas zona glomerulosa was negative for inhibin cc. Adrenal medullary cells were also negative for inhibin a. Results were similar also in the hyperplastic adrenal cortex. Most of the adrenocortical adenomas possessed weak and focal staining for inhibin a, but strong staining was noted in all virilizing tumors. Adrenocortical carcinomas showed variable immunostaining for inhibin a. Regardless of hormonal activity, adrenocortical carcinomas were either strongly positive or completely negative for inhibin a.
DISCUSSION
In our study, strong immunoreactivity was detected in zona reticularis of normal and hyperplastic adrenal cortex, as well as in virilizing adrenocortical adenomas. However, outer layers of normal adrenal cortex and mineralocorticoid- or glucocorticoid-producing adrenocortical adenomas were only weakly positive or even completely negative for inhibin a. This data suggests a zone specific expression of inhibin a, i.e. its expression is high in androgen producing adrenocortical cells. High inhibin a expression in normal adrenal cortex and adrenocortical adenomas can be used as a marker for androgen production.
Endocr Res Downloaded from informahealthcare.com by Queen’s University on 07/27/13 For personal use only.
Previous reports on inhibin & immunoreactivity in adrenal neoplasms suggested a consistent positive expression in all adrenocortical tumors (4,5). However, our data suggests a hormonal activity-dependent expression in adrenocortical adenomas and hormonal activity-independent expression in adrenocortical carcinomas. Also completely negative adenomas and carcinomas do exist, unlike what has been previously reported.
REFERENCES
1. Voutilainen R. 1995 Eur J Endocrinol 132: 290-291.
2. Nishi Y, Haji M, Takayanagi R, Yanase T, Ikuyama S, Nawata H. 1995 Eur J Endocrinol 132: 292-299.
3. Matzuk MM, Finegold M J, Su J-G J, Hsueh A J W, Bradley A. 1992 Nature 360: 313-319.
4. Chivite A, Matias-Guiu X, Pons C, Algaba F, Prat J. 1998 Appl Immunohistochem 6: 42-49.
5. McCluggage W G, Burton J, Maxwell P, Sloan J M. 1998 J Clin Pathol 51: 114-116.