ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2001) 2 P83

Expression of Orexin-A and and functional Orexin type-2 receptors in human fetal and adult adrenals: Implications in adrenal function and energy homeostatsis

E Karteris, EW Hillhouse & HS Randeva

Department of Biological Sciences, University of Warwick, Coventry, UK.

Recently, two new peptides named Orexin-A and Orexin-B, have been implicated in the regulation of feeding behaviour. Studies in starved rats have shown that catabolic activity quickly predominates, reinforced by elevated corticosterone, not driven by ACTH, implicating adrenal activity as a metabolic regulator. In view of these findings, we sought to investigate whether orexin and orexin receptors are present in human fetal and adult adrenals, and therefore may be implicated in hormonal regulation and energy homeostasis outside the CNS. RT-PCR, Western blotting, and immunostaining analysis confirmed the expression of the orexin type-2 receptor (OX2R). Immunoblotting analysis also detected the presence of the prepro-orexin and orexin-A in both tissues. Using [a-32P] GTP-azidoanilide (GTP-AA) and peptide antisera raised against G-protein a-subunits, we studied coupling of OX2R to G-proteins in both tissues. Treatment of adult adrenal membranes with Orexin-A increased the labelling of Gs, Gq, and to a less degree Gi but not Go, whereas OX2R couples only to Gs and Gi in fetal adrenal membranes.

In summary, our findings strongly suggest that orexin type-2 receptors are present in human fetal and adult adrenals. The concept that the peptide acting via these receptors in an autocrine manner, is responsible for steroidogenesis and energy balance is attractive. Moreover, in fetuses, orexin might play a key-role in the development of the embryo by influencing its feeding behaviour and nutritional status in preparation of the fetus for extrauterine life.

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