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Submitted on December 20, 2005
Accepted on January 25, 2006
Department of Environmental & Biomolecular Systems, OGI School of Science & Engineering (J.X., R.L.S.), Beaverton, Oregon 97006; Division of Reproductive Sciences, Oregon National Primate Research Center (J.X., J.D.H, R.L.S.), Beaverton, Oregon 97006; and Department of Obstetrics/Gynecology, and Physiology/Pharmacology, Oregon Health & Science University (J.D.H, R.L.S.), Portland, Oregon 97239
* To whom correspondence should be addressed. 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) following LH withdrawal.
Objective: Determine if other components of the CRH/urocortin(UCN)-receptor(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 (day 3-5 post LH surge) to very late (day 18-19) luteal phase and from controls or animals receiving GnRH antagonist (Antide, 3 mg/kg BW). 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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