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Prepro-Orexin and Orexin Receptor mRNAs Are Differentially Expressed in Peripheral Tissues of Male and Female Rats

Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University Lübeck, D-23538 Lübeck, Germany

Address all correspondence and requests for reprints to: Olaf Jöhren, Ph.D., Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. E-mail: joehren{at}medinf.mu-luebeck.de

Orexins are produced specifically by neurons located in the lateral hypothalamus. Recent results suggested peripheral actions of orexins. Therefore, we analyzed the mRNA expression of prepro-orexin and the orexin receptor subtypes OX₁ and OX₂ in peripheral rat tissues. Using real-time quantitative RT-PCR we detected significant amounts of prepro-orexin mRNA in testis, but not in ovaries. OX₁ receptor mRNA was highly expressed in the brain and at lower levels in the pituitary gland. Only small amounts of OX₁ receptor mRNA were found in other tissues such as kidney, adrenal, thyroid, testis, ovaries, and jejunum. Very high levels of OX₂ receptor mRNA, 4-fold higher than in brain, were found in adrenal glands of male rats. Low amounts of OX₂ receptor mRNA were present in lung and pituitary. In adrenal glands, OX₂ receptor mRNA was localized in the zona glomerulosa and reticularis by in situ hybridization, indicating a role in adrenal steroid synthesis and/or release. OX₁ receptor mRNA in the pituitary and OX₂ receptor mRNA in the adrenal gland were much higher in male than in female rats. In the hypothalamus, OX₁ receptor mRNA was slightly elevated in female rats. The differential mRNA expression of orexin receptor subtypes in peripheral organs indicates discrete peripheral effects of orexins and the existence of a peripheral orexin system. This is supported by the detection of orexin A in rat plasma. Moreover, the sexually dimorphic expression of OX₁ and OX₂ receptors in the hypothalamus, pituitary, and adrenal glands suggests gender-specific roles of orexins in the control of endocrine functions.