Abstract
The peptides orexin A and B are synthesized by neurons located in the lateral hypothalamus and act at two receptor subtypes, namely OX1 and OX2. Besides their stimulatory effects on feeding, orexins are involved in the regulation of the autonomic nervous system, sleep-wakefulness and neuroendocrine functions. Recently, we found very high amounts of OX2 receptor mRNA in the adrenal gland, which where significantly higher in male rats compared to female rats. To investigate a possible influence of gonadal steroids on the expression of adrenal orexin receptors, we analyzed the effect of gonadectomy and testosterone or estradiol replacement on adrenal OX1 and OX2 receptor mRNA expression in male and female rats by quantitative real-time RT-PCR and in situ hybridization. Further, we examined the effect of orexin A on the synthesis of corticosterone in isolated, perfused adrenal glands of male and female rats. While the mRNA levels of adrenal OX1 receptors were low, high amounts of OX2 receptor mRNA were detected in both, male and female rats. Orchidectomy decreased the amounts of OX2 receptor mRNA in male rats. In contrast, in adrenals of ovariectomized female rats, OX2 receptor mRNA levels were increased compared to sham-operated rats. Substitution with testosterone or estradiol reversed the effects of gonadectomy. In situ hybridization revealed much higher levels of OX2 receptor mRNA in the adrenal cortex than in the medulla and confirmed the regulation of OX2 receptor mRNA by gonadal steroids in the adrenal cortex of both sexes. Stimulation of perfused adrenal glands from male and female rats with orexin A significantly increased the perfusate levels of corticosterone. The effect started 50min after the onset of orexin A treatment. In summary, we demonstrate the differential regulation of OX2 receptor expression in the adrenal cortex by gonadal steroids, which may cause the sexually dimorphic expression of these receptors. Orexins are suggested to stimulate the production of corticosterone in male and female rats. The late corticosterone response indicates a possible influence of orexins on the expression of corticosteroid-synthesizing enzymes.
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