Inhibins and activins: Their roles in the adrenal gland and the development of adrenocortical tumors

The adrenal gland is composed of two separate endocrine tissues that control a multitude of bodily functions in their adaptation to external and internal stressors through hormone secretion. The functions of the adrenal gland are regulated by circulating, neural and local factors that ensure proper cell growth and hormone production. Activins and inhibins are among the locally expressed growth factors affecting adrenal cell function. They have been found to influence several aspects of adrenal cell development, adrenocortical steroidogenesis, adrenocortical tumor formation and adrenomedullary cell differentiation. Especially the finding that inhibin α-subunit knockout mice develop adrenocortical carcinomas after gonadectomy has prompted research on the physiological and pathophysiological roles of activin and inhibin in the adrenal cortex. It is now clear that both peptides control adrenocortical physiology and are involved in adrenocortical tumorigenesis at multiple levels, both in murine models as well as in human patients.

► Activin and inhibin affect adrenal development, growth, function and tumorigenesis.
► Activin decreases adrenal cell growth and cortisol and adrenal androgen production.
► Gonadectomized Inha −/− mice develop adrenal tumors with a gonadal phenotype.
► TGF-β2 and gonadotrophins induce cyclin D2-dependent cell growth in these tumors.
► In human ACC, INHA displays both oncogenic and tumor-suppressive characteristics.