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Orexins are peptides controlling feeding, sleep, and neuroendocrine functions. They are synthesized by the hypothalamus with projections throughout the brain. Orexins and their orexin 1 (OX₁) and orexin 2 receptors (OX₂) are present outside the central nervous system. Here the expression of preproorexin (PPO), OX₁, and OX₂ was studied in rat ovaries. PPO, OX₁, and OX₂ were determined by quantitative real-time RT-PCR in ovaries of cycling Sprague-Dawley rats on all days of the cycle. Serum hormones and food consumption were determined. Ovarian OX₁ and OX₂ expression was then studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 1400 and 1900 with a selective OX₁ antagonist (SB-334867-A) and/or a selective OX₂ antagonist (JNJ-10397049), and hormone levels, ovulation, and ovarian histology were studied. Both receptors' expression increased in …