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Expression and Role of the Corticotropin-Releasing Hormone/Urocortin-Receptor-Binding Protein System in the Primate Corpus Luteum during the Menstrual Cycle

Divisions of Neuroscience (J.X.) and Reproductive Sciences (F.X., J.D.H., T.A.M., R.L.S.), Oregon National Primate Research Center, Beaverton, Oregon 97006; and Departments of Obstetrics and Gynecology (J.D.H., R.L.S.) and Physiology and Pharmacology (R.L.S.), Oregon Health & Science University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Richard L. Stouffer, Ph.D., Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006. E-mail: stouffri{at}ohsu.edu.

CRH/urocortin-receptor-binding protein (CRH/UCN-R-BP) mRNAs are dynamically expressed in the primate ovary during the menstrual cycle. Therefore, studies were designed to localize CRH/UCN-R-BP mRNAs to ovarian cell types, quantitate protein expression during the corpus luteum (CL) lifespan, and investigate the role of this system in the macaque ovary at midcycle. Monkey ovaries were removed during the preovulatory phase and through the luteal phase to localize CRH/UCN-R-BP mRNAs by in situ hybridization and determine their protein levels in CL by Western blotting. Also, vehicle or a CRH receptor antagonist (astressin) was injected into the preovulatory follicle; daily serum samples were analyzed for hormone levels, and ovaries were removed on d 9 of the luteal phase for histological analysis. There was minimal ligand mRNA staining, whereas receptor and CRHBP was detected in the granulosa and theca cells of the preovulatory follicle. However, ligand and receptor mRNA staining was appreciable in luteal cells of the CL during the early luteal phase (ECL) and diminished in the late luteal phase (LCL). CRHBP staining was low in the ECL and increased markedly in the LCL. Ligand and receptor protein expression was also highest during ECL, whereas CRHBP expression was highest at the LCL. Although astressin injection did not prevent follicle rupture, progesterone levels were significantly less by the mid-luteal phase, and estradiol levels never increased above baseline during the CL lifespan. Histological indices of cell degeneration were observed in the astressin-treated CL. Thus, CRH/UCN-R-BP components are expressed in an ovarian cell-specific manner. The expression pattern and results from antagonist injection are consistent with the hypothesis that CRH/UCN-R activation promotes luteal development and/or structure-function in monkeys during the menstrual cycle.