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Dynamic Expression and Regulation of the Corticotropin-Releasing Hormone/Urocortin-Receptor-Binding Protein System in the Primate Ovary during the Menstrual Cycle

Department of Environmental and Biomolecular Systems, OGI School of Science and Engineering (J.X., R.L.S.), and Division of Reproductive Sciences, Oregon National Primate Research Center (J.X., J.D.H., R.L.S.), Beaverton, Oregon 97006; and Departments of Obstetrics/Gynecology and Physiology/Pharmacology, Oregon Health and Science University (J.D.H., R.L.S.), Portland, Oregon 97239

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

Context: Microarray analysis discovered that mRNA for CRH-binding protein (CRHBP) increased significantly in the primate corpus luteum (CL) after LH withdrawal.

Objective: Our objective was to determine whether other components of the CRH/urocortin-receptor-binding protein (UCN-R-BP) system are expressed in the CL during the menstrual cycle and regulated by LH.

Design: CL were collected from monkeys during the early (d 3–5 after the LH surge) to very late (d 18–19) luteal phase and from controls or animals receiving GnRH antagonist (Antide, 3 mg/kg body weight). CRH/UCN-R-BP system components were quantitated for mRNA levels by real-time PCR and analyzed for protein localization by immunohistochemistry.

Results: All genes encoding the CRH/UCN-R-BP system, except for UCN3, were expressed in the CL. CRH mRNA levels did not change during the luteal phase, whereas expression of UCN, UCN2, CRHR1, and CRHR2 was maximal at early or mid luteal phase before declining (P < 0.05) at the later stages. CRHBP mRNA levels were lowest at mid and increased (P < 0.05) in the late luteal phase. Suppressing gonadotropin secretion reduced UCN2 (P < 0.05) and increased CRHBP (P < 0.05) mRNA levels, without altering the expression of other ligands or receptors. CRH, UCN, UCN2 and their receptors were localized to the granulosa-lutein cells of the CL, whereas CRHBP was limited to the theca and theca-lutein cells of the preovulatory follicle and CL.

Conclusions: A local CRH/UCN-R-BP system exists in the macaque CL that is dynamically expressed and LH regulated during the luteal phase of the menstrual cycle. Ligand-receptor activity may regulate luteal structure-function, at this point in an unknown manner, in primates.

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