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Urocortin and Corticotropin-Releasing Factor Receptor Expression in Normal Cycling Human Ovaries¹

Departments of Pathology (Y.M., T.S., H.S.), Psychosomatic Medicine (Y.M., A.T., M.H.), Internal Medicine (K.To.), and Molecular Biology (K.Ta.), Tohoku University School of Medicine, Sendai 980-8575; Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine (N.S.), Ube 755-8505; and Second Division, Department of Medicine, Hamamatsu University School of Medicine (Y.O.), Hamamatsu 431-3192, Japan

Address all correspondence and requests for reprints to: Yasunari Muramatsu, M.D., Department of Pathology, Tohoku University School of Medicine, 2–1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail: murayasu{at}patholo2.med.tohoku.ac.jp

Urocortin is a member of the CRF neuropeptide family and has a 43% homology to CRF in amino acid sequence. Urocortin has been found to bind with high affinity to CRF receptors. CRF has been detected in the human ovary and has been demonstrated to suppress ovarian steroidogenesis in vitro. In this study we examined urocortin and CRF receptor expression in normal cycling human ovaries, using immunohistochemistry and RT-PCR. Normal cycling human ovaries were obtained at oophorectomy and hysterectomy from patients who underwent surgery for cervical cancer or myoma uteri. Intense urocortin immunoreactivity was detected in luteinized thecal cells of regressing corpora lutea, in which only luteinized thecal cells have the capacity for steroidogenesis. Immunoreactive urocortin was also detected in luteinized granulosa and thecal cells of functioning corpora lutea, in which both cell components are capable of producing steroids. RT-PCR analyses revealed that messenger ribonucleic acid levels for urocortin, CRF, and CRF receptor type 1 and type 2 were significantly higher in the regressing corpus luteum than in the functioning corpus luteum. The spatial and temporal immunolocalization patterns of CRF receptor were similar to those of urocortin. These results suggest that urocortin is locally synthesized in steroidogenic luteal cells and acts on them as an autocrine and/or paracrine regulator of ovarian steroidogenesis, especially during luteal regression.

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