Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats

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.