Gastric estrogen directly induces ghrelin expression and production in the rat stomach.
Ghrelin, an endogenous ligand for the GH secretagogue receptor, is predominantly produced in the stomach. Little is known about the regulation mechanism of gastric ghrelin. Here, we report that estrogen synthesized in the stomach induces rat gastric ghrelin gene expression and production. We established a gastric ghrelin cell enrichment method using Percoll centrifugation and then studied the effect of estrogen and/or its antagonist on ghrelin expression and production. Treatment with estrogen for 8 h significantly increased the level of ghrelin expression, and ICI-182 780, an estrogen receptor (ER) antagonist, completely reversed this effect. Reverse transcriptase-PCR analysis clearly showed that ERalpha and aromatase are expressed in the female rat stomach. Moreover, treatment with an aromatase inhibitor, 4-hydro-xyandrostenedione (formestane), significantly decreased the level of ghrelin mRNA expression in minced stomach tissue. In vivo studies revealed that the ghrelin mRNA expression and production did not change in gonadectomized rat 3 weeks after surgery. These results strongly suggest that estrogen produced in the stomach directly induces ghrelin expression and production in both female and male rat stomachs.
Sakata
Ichiro
I
Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan.
Tanaka
Toru
T
Yamazaki
Mami
M
Tanizaki
Takashi
T
Zheng
Zhao
Z
Sakai
Takafumi
T
D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism*; D054439:Ghrelin; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D036361:Peptide Hormones / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects
D047072:Aromatase Inhibitors; D047628:Estrogen Receptor alpha; D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase; C014594:formestane