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BOR - Papers in Press, published online ahead of print April 30, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.068403
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Submitted February 14, 2008
Returned for revision March 25, 2008
Accepted April 22, 2008

Pregnancy


Gastrin-Releasing Peptide (GRP) in the Ovine Uterus: Regulation by Interferon Tau and Progesterone

Gwonhwa Song , M. Carey Satterfield , Jinyoung Kim , Fuller W. Bazer , and Thomas E. Spencer *

* To whom correspondence should be addressed. E-mail: tspencer{at}tamu.edu.

Abstract
Gastrin-releasing peptide (GRP) is abundantly expressed by endometrial glands of the ovine uterus and processed into different bioactive peptides, including GRP1-27, GRP18-27, and a C-terminus, that affect cell proliferation and migration. However, little information is available concerning the hormonal regulation of endometrial GRP and expression of GRP receptors in the ovine endometrium and conceptus. These studies determined the effects of pregnancy, progesterone (P4), interferon tau (IFNT), placental lactogen (CSH1) and growth hormone (GH) on expression of GRP in the endometrium and GRP receptors (GRPR, NMBR, BRS3) in the endometrium, conceptus and placenta. In pregnant ewes, GRP mRNA and protein were first detected predominantly in endometrial glands after Day 10 and were abundant from Days 18 to 120 of gestation. Treatment with IFNT and progesterone, but not CSH1 or GH, stimulated GRP expression in the endometrial glands. Western blot analyses identified proGRP in uterine luminal fluid and allantoic fluid from Day 80 unilateral pregnant ewes, but not in uterine luminal fluid of either cyclic or early pregnant ewes. GRPR mRNA was very low in the Day 18 conceptus and undetectable in the endometrium and placenta; NMBR and BRS3 mRNAs were undetectable in ovine uteroplacental tissues. Collectively, the present studies validate GRP as a novel IFNT-stimulated gene in the glands of the ovine uterus, revealed that IFNT induction of GRP is dependent on P4, and found that exposure of the ovine uterus to P4 for 20 days induces GRP expression in endometrial glands.

Key words: Implantation • Placenta • Progesterone • Trophoblast • Uterus





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