The expression of inhibin/activin subunits in the human adrenal cortex and its tumours

Abstract

Inhibins and activins are dimeric proteins of the transforming growth factor-β superfamily which have been shown to be expressed in the adrenal cortex. Recent studies have suggested a role for these peptides in the pathogenesis and/or function of adrenal tumours. To investigate further their physiological and pathological roles, we have documented immunoreactivity for inhibin α, βA and βB subunits in normal adult and fetal human adrenals, in hyperplastic adrenals and in adrenal tumours. In the normal and hyperplastic adult gland, diffuse immunopositivity was demonstrated for β subunits, suggesting that activins (ββ dimers) can be expressed in all zones. Inhibin α was limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia, supporting a role for ACTH in the regulation of expression, and suggesting that expression of inhibins (αβ dimers) is restricted. Immunopositivity for all three subunits was seen in both fetal and definitive zones of the fetal cortex, indicating that both inhibins and activins could be expressed in both. Immunopositivity for all three subunits was seen in most adrenocortical tumours. Loss of immunopositivity for inhibin α in a subgroup of carcinomas might indicate a role in tumour progression. The greater intensity of staining for inhibin α in tumours associated with Cushing's syndrome again suggests a link with cortisol production.