High impact information on GRP

• At term, intense immunohistochemical staining for GRPLI occurred in the endometrial epithelial cells, and the term ovine uterus also contained abundant GRP messenger RNA (mRNA) [1].
• We conclude that during pregnancy, the ovine uterus produces considerable quantities of GRP, which may play an important but hitherto unrecognized role in utero-placental development and possibly in fetal development after transfer to the fetus [1].
• In contrast, GRP mRNA was not detected in fetal membranes [1].
• As previous studies suggested the GRPLI entity to be of greater molecular size than GRP-(1-27), we deduced the primary structure of ovine uterus GRP by sequencing a complementary DNA clone isolated from a complementary DNA library constructed from term ovine uterus polyadenylated RNA [1].
• Thereafter, levels remained elevated until term, but 3 months postpartum, GRP mRNA levels were greatly reduced [1].

Biological context of GRP

• However, during luteolysis and oestrus the major peak of GRP immunoreactivity extracted from endometrial tissue was larger than GRP(1-27) and similar to that seen previously in the gravid ovine endometrium [2].
• The larger molecular size [greater than GRP (1-27)] of this GRP-LI entity is not due to a GRP binding protein nor to a C-terminal extension of GRP [3].
• Fetal and maternal plasma GRP were elevated compared with nonpregnant ewes, falling sharply after parturition [4].
• Mammalian gastrin-releasing peptides (GRP) are present in female reproductive tissues and stimulate uterine contraction and DNA synthesis in the endometrium [4].
• At 117-119 days of gestation saline (n = 5), amniotic fluid (n = 5), colostral whey (n = 5), milk whey (n = 5) or gastrin-releasing peptide (3.6 nmol day(-1), n = 6), was infused for 7 days (4 x 20 mL day(-1)), or no infusion was given (ligated group, n = 6) [5].

Anatomical context of GRP

• We have previously shown that the peptide immunoreactivity related closely to the mitogen GRP is expressed by the pregnant ovine endometrium during the final third of pregnancy [6].
• Secreted GRP peptide levels rise 10 fold just prior to implantation, while endometrial peptide and mRNA concentrations increase 4 and 13 fold respectively between day 17 and 20, immediately following attachment and corresponding to the onset of placentome development [6].
• Mammalian members of the bombesin-like peptide family (gastrin releasing peptides; GRP) have been localized in the ovine median eminence and in hypophysial-portal blood, suggesting a role in the regulation of anterior pituitary function [7].
• GRP has multiple complex stimulatory effects on the endocrine pancreas, and there exist species-dependent differences in responses, which affect the potency and spectrum of the hormone-releasing activity of GRP [8].
• No GRP mRNA was detected in the amnion or chorioallantois [9].

Associations of GRP with chemical compounds

• We suggest that in species such as sheep, GRP is a potentiator of glucose-stimulated insulin release [10].
• The response to GRP is less in pregnant than in nonpregnant animals, and this attenuation is mimicked in nonpregnant animals treated with E2 plus P4 [10].
• These studies demonstrate that, in sheep, the synthesis, storage and secretion of GRP are differentially affected by oestrogen and progesterone [11].
• In this study we have shown that although bombesin cannot stimulate ACTH secretion alone, it potentiates release by ovine CRF, an effect blocked by the GRP receptor antagonist D-Tyr6bombesin (6-13) propylamide [7].

Regulatory relationships of GRP

• Further studies are required to determine the precise anatomical relation of GRP-containing nerve fibers to islet cells and to elucidate the pathways by which GRP activates endocrine pancreatic hormone release [8].

Other interactions of GRP

• Endometrial genes increased by pregnancy and P4 and/or IFNT include B2M, CTSL, CXCL10, G1P3, GRP, IFI27, IFIT1, IFITM3, LGALS15, MX1, POSTN, RSAD2, and STAT5A [12].
• Changes in GRP mRNA expression did not correlate with changes in endometrial expression of mRNA for oestrogen receptor alpha, oestrogen receptor beta and the progesterone receptor [11].
• Concurrent elevation of fundic somatostatin prevents gastrin stimulation by GRP [13].

Analytical, diagnostic and therapeutic context of GRP

• In situ hybridization localized GRP synthesis to the epithelial cells of the uterine glands at day 16 of the oestrous cycle and at days 17, 20, 40 and 50 of pregnancy [2].
• Immunohistochemistry localized GRP peptide to the apical cytoplasm of uterine glandular epithelial cells at day 16 of the oestrous cycle [2].
• 2. Foetal metabolic clearance rate of GRP was significantly increased (P < 0.05) compared to the non-pregnant ewe (19.9 +/- 2.6 (s.e.m.) and 11.8 +/- 2.0 mL/min per kg, respectively) [9].
• To determine the local source of SOM, GRP was then infused into nonimmunized sheep with cannulas draining blood from the fundus and antrum [13].
• Gel filtration and reverse-phase high pressure liquid chromatography (HPLC) demonstrated the existence of two molecular forms of BLI, which co-eluted with porcine gastrin releasing peptide (GRP)1-27 and GRP18-27 in a molar ratio of 1:2 [14].

References