Presence of corticotropin-releasing-hormone receptor on adrenocortical cells

Abstract

Corticotropin-releasing hormone (CRH) is not only the principal regulator of the stress system but also exerts profound actions on peripheral tissues. Its control over adrenal steroidogenesis is accomplished through activation of the hypothalamo-pituitary-adrenal (HPA) axis and the sympathoadrenal (SA) system. However, there is growing evidence for a direct involvement in control of adrenal function on the level of the adrenal gland. Most effects of CRH on adrenal steroidogenesis have been attributed to a paracrine action of medulla-derived corticotropin (ACTH)-like factors in a lokal CRH receptor / ACTH system. But growing evidence for a direct action of CRH on the adrenal cortex also exists. Therefore, we studied the distribution of immunoreactive CRH-receptor protein employing immunohistochemistry of paraffin-embedded sections of three normal human adrenal glands, four adrenocortical and two adrenomedullary tumors. In addition, we examined expression of CRH type 1 receptor mRNA in microdissected preparations of the adrenal cortex from two normal human adrenal glands, in two medulla-free adrenal incidentalomas, one cortisol-producing adrenal adenoma and in two cortex-free pheochromocytomas. While adrenocortical cells could be immunolabelled with the antibody directed to CRH type 1/2 receptors in normal human adrenal glands in all three zones and in adrenocortical tumors, adrenal chromaffin cells could not, neither in sections of normal human adrenals nor in pheochromocytomas. In addition, the data document a higher expression of the type 1 CRH receptor mRNA in the preparations which were rich in adrenocortical cells and in preparations of adrenocortical tumors in comparence to the tissue obtained from pheochromocytomas. We conclude that adrenocortical cells exhibit a higher expression of CRH receptors than adrenal chromaffin cells as shown on the mRNA and protein level. The data support the hypothesis of a direct action of CRH on adrenocortical cells in addition to its action via an intraadrenal CRH receptor / ACTH system.