Exp Clin Endocrinol Diabetes 2003; 111 - P21
DOI: 10.1055/s-2003-817563

Orexin (hypocretin) receptor subtypes are differentially expressed in the hypothalamic-pituitary-adrenal axis of rat models of obesity and diabetes

J Gremmels 1, O Jöhren 1, F Qadri 1, A Dendorfer 1, P Dominiak 1
  • 1Institute of Experimental and Clinical Pharmacology and Toxicology, Luebeck, Germany

Orexins (hypocretins) are hypothalamic peptides which stimulate food intake and which are involved in the regulation of energy homeostasis. Besides the control of feeding behavior orexins were implicated in the regulation of neuroendocrine and autonomic functions. Orexins activate two G protein-coupled receptors, OX1 and OX2, which are widely expressed in the rat brain. Recent data showed the expression of orexin receptors in hypothalamic-pituitary-adrenal (HPA) axis and suggested specific actions of orexins at the pituitary and adrenal glands. To further evaluate the role of orexin in the HPA axis we investigated the mRNA expression of prepro-orexin (PPO) and orexin receptors in the HPA axis of obese Zucker fatty (ZUCKER) rats, Zucker diabetic fatty (ZDF) rats showing type-2 like diabetes, and streptozotocin-injected (STZ) rats showing type-1 like diabetes. To characterize the rat models, plasma insulin, leptin, and glucose levels were determined. PPO, as well as OX1 and OX2 receptor levels were analyzed by quantitative real-time PCR. Hypothalamic PPO mRNA levels were significantly reduced in STZ but not in ZUCKER or ZDF rats when compared to the respective lean/non-diabetic control rats. In addition, no differences were found in the mRNA levels of hypothalamic OX1 and OX2 receptors in ZUCKER, ZDF, or STZ rats in comparison to control rats. However, pituitary and adrenal OX1 receptor mRNA levels were elevated in ZDF and STZ rats but not in ZUCKER rats when compared to control rats. In contrast, adrenal mRNA levels of OX2 receptors were significantly reduced in all groups. The enhanced mRNA expression of pituitary and adrenal OX1 receptors in ZDF and STZ rats parallels the rise in plasma glucose in these groups and may reflect a functional relationship. The down regulation of adrenal OX2 receptors might be due to leptin resistance in ZUCKER and ZDF rats and to very low leptin levels in STZ rats.