Adrenocortical Cells are the Site of Secretion and Action of Insulin-Like Growth Factors and TNF-Alpha

Insulin-like growth factors I and/or II are expressed in adrenal cells, and modulate their proliferation and steroid hormone synthesis suggesting that they may function as paracrine/autocrine factors. In some species, at least ACTH induces insulin-like growth factor synthesis. Thus, these peptide growth factors mediate at least some of the effects of ACTH on adrenocortical cell proliferation and differentiation. Human fetal adrenals express insulin-like growth factor II gene abundantly and ACTH-dependently, while in adult adrenals, the expression is low and no ACTH dependent regulation has been demonstrated. Hormonally active adrenocortical carcinomas and virilizing adenomas express insulin-like growth factor II gene abundantly. This phenomenon is associated with reduced expression of two putative tumor suppressor genes (H19 and p57^KIP2) locating on the same genomically imprinted locus on human chromosome 11p15.5. Tumor necrosis factor-alpha belongs to the cytokines which modulate hypothalamic-pituitary-adrenal axis. It is a potent inducer of ACTH secretion but, at the adrenal level, it seems to mainly inhibit ACTH-induced steroidogenesis and also insulin-like growth factor II expression. It is produced in adrenocortical steroidogenic cells in addition to macrophages, which suggests that tumor necrosis factor-alpha may have some autocrine/paracrine functions in the adrenal cortex.

Key words

Steroidogenesis - Adrenal - Imprinting - Cytokines - Tumor Suppressor - H19 - p57^KIP2