Ghrelin and ghrelin receptor in mouse uterus: Cyclic change during estrous cycle and regulation by ovarian steorids.

Abstract

Ghrelin has been recently identified as the endogenous ligand for the GH-secretagogue receptor (GHS-R) and shown to stimulate the release of GH from somatotrophs of the anterior pituitary through the GHS-R. Recent studies have revealed that ghrelin has many physiological functions, including the regulation of gastric function, an antiproliferative effect, cardiovascular actions, and stimulation of insulin secretion. Present study determined the changes of ghrelin and GHS-R gene expression in mouse uterus during the estrous cycle by real-time PCR and confocal microscopy. Also, we investigated the effects of 17beta-estradiol and progesterone on the expression of ghrelin and GHS-R. In cyclic mouse endometrium, ghrelin and GHS-R immunoreactivity was found in luminal as well as glandular epithelia and stroma. Ghrelin and GHS-R immunoreactivity was the most intensive in luminal as well as glandular epithelia at proestrous cycle. In stroma ghrelin immunoreactivity was the most strong at diestrous stage but GHS-R immunoreactivity was the most strong at estrous stage. Coincidently, realtime PCR analysis revealed that uterine ghrelin and GHS-R mRNA level was the highest at proestrous stage. In order to determine the effect of ovarian steroids on the expression of ghrelin and GHS-R genes, ovariectomized (OVX) mice were single injected with 17beta-estradiol (E2, 0.3 or 1 μg), progesterone (P4, 1 mg) and a mixture of P4 (1 mg) and E2 (0.3 μg). After 24h ghrelin mRNA level was significantly increased in P4 and high dose E2 (1 μg) treated mice compared with vehicle (sesame oil) control OVX mice. Coincidently, ghrelin immunoreactivity was increased in luminal and glandular endometrium. In OVX mice uterus, GHS-R mRNA level was significantly decreased by E2 or P4. In summary, the expression of ghrelin and GHS-R was differentially regulated by ovarian steroids in mouse uterine endometrium. Ghrelin may act as a novel paracrine/autocrine factor in cross-talk between endometrial epithelia and stromal cells and between the endometrium and implanting embryos. (poster)