Expression of orexin-A and functional orexin type 2 receptors in the humanadult adrenals: Implications for adrenal function and energy homeostasis

The hypothalamic peptides, orexin-A and orexin-B, have been implicated in t he regulation of feeding behavior. In starved rats catabolic activity quick ly predominates, reinforced by elevated corticosterone, independent of ACTH , implicating adrenal activity as a metabolic regulator. In view of these f indings, we investigated whether orexin and orexin receptors are present in human adult adrenals and might therefore be implicated in hormonal regulat ion and energy homeostasis outside the central nervous system. RT-PCR, fluo rescent in situ hybridization, immunoblotting, and immunostaining analysis confirmed the expression of the orexin type 2 receptor, but not of orexin t ype 1 receptor, in the adrenal cortex. Immunoblotting analysis also detecte d the presence of the prepro-orexin and its cleaved product orexin-A. Treat ment of adult adrenal membranes with orexin-A increased the labeling of G(s ), G(q), and, to a lesser degree, G(i), but not G(o). Stimulation with orex in-A induced cAMP and IP3 production in a dose-dependent manner. The data p resented here provide conclusive evidence for the presence of orexin-A and orexin type 2 receptors in human adult adrenal glands. At the moment the fu nctional relevance of this is uncertain. However, it is known that both ore xin-A and orexin-B can induce corticosterone production in dispersed rat ad renocortical cells. Our data provide further evidence for a functional link between orexogenic signals and adrenal function. The concept that the pept ide acting via these receptors in the adult adrenal is responsible for ster oidogenesis and energy balance is attractive.