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Gonadal Steroids Differentially Regulate the Messenger Ribonucleic Acid Expression of Pituitary Orexin Type 1 Receptors and Adrenal Orexin Type 2 Receptors

Institute of Experimental and Clinical Pharmacology and Toxicology, University Clinic 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, University Clinic Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. E-mail: Joehren{at}medinf.mu-luebeck.de.

Hypothalamic prepro-orexin as well as pituitary and adrenal orexin receptors are gender-specifically expressed. To assess the regulation by gonadal steroids, we investigated the effect of 17ß-estradiol in female and of testosterone in male rats on prepro-orexin and orexin receptor mRNA expression. Rats were either sham-operated or gonadectomized and subsequently treated with placebo, 17ß-estradiol, or testosterone for 21 d. Tissue mRNA levels of prepro-orexin, orexin type-1 (OX₁), and orexin type-2 (OX₂) receptors were measured using quantitative real-time RT-PCR.

In female rats, pituitary OX₁ receptor mRNA levels were increased 12-fold after ovariectomy compared with sham- operated rats. The increase of pituitary OX₁ receptor mRNA was inhibited by treatment with 17ß-estradiol. Adrenal mRNA levels of OX₂ receptors in ovariectomized rats were increased 2-fold compared with sham-operated rats and were also reduced by treatment with 17ß-estradiol. In male rats, orchidectomy increased the mRNA levels of pituitary OX₁ receptors compared with sham-operated rats. In contrast, adrenal OX₂ receptor mRNA was reduced after orchidectomy. Testosterone treatment reversed the effect of orchidectomy on pituitary OX₁ and adrenal OX₂ receptors. In the hypothalamus, no differences were found in the mRNA levels of prepro-orexin, OX₁, and OX₂ receptors between sham-operated, placebo-treated, and steroid-treated female or male rats.

Our results indicate that gonadal steroids differentially regulate pituitary OX₁ receptors and adrenal OX₂ receptors in male and female rats and may contribute to specific sex- dependent neuroendocrine and endocrine actions of orexins.

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