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 hypotha lamus. Recent results suggested peripheral actions of orexins. Therefore, w e analyzed the mRNA expression of prepro-orexin and the orexin receptor sub types OX1 and OX2 in peripheral rat tissues. Using real-time quantitative R T-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 mRN A were found in other tissues such as kidney, adrenal, thyroid, testis, ova ries, and jejunum. Very high levels of OX2 receptor mRNA, 4-fold higher tha n in brain, were found in adrenal glands of male rats. Low amounts of OX2 r eceptor mRNA were present in lung and pituitary. In adrenal glands, OX2 rec eptor mRNA was localized in the zona glomerulosa and reticularis by in situ hybridization, indicating a role in adrenal steroid synthesis and/or relea se. 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, O X1 receptor mRNA was slightly elevated in female rats. The differential mRN A expression of orexin receptor subtypes in peripheral organs indicates dis crete peripheral effects of orexins and the existence of a peripheral orexi n system. This is supported by the detection of orexin A in rat plasma. Mor eover, the sexually dimorphic expression of OX1 and OX2 receptors in the hy pothalamus, pituitary, and adrenal glands suggests gender-specific roles of orexins in the control of endocrine functions.