Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats.
Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R), stimulates a release of growth hormone, prolactin and adrenocorticotropic hormone. Also, ghrelin increases food intake in adult rats and humans and exhibits gastroprotective effect against experimental ulcers induced by ethanol or stress. The aim of present study was to examine the influence of ghrelin administration on gastric and duodenal growth and expression of pepsin and enterokinase in young mature rats with intact or removed pituitary.


METHODS
Two week after sham operation or hypophysectomy, eight week old Wistar male rats were treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a day for 4 days. Expression of pepsin in the stomach and enterokinase in the duodenum was evaluated by real-time PCR.


RESULTS
In animals with intact pituitary, treatment with ghrelin increased food intake, body weight gain and serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These effects were accompanied with stimulation of gastric and duodenal growth. It was recognized as the significant increase in gastric and duodenal weight and mucosal DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg caused maximal growth-promoting effect. In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum. Hypophysectomy alone lowered serum concentration of growth hormone under the detection limit and reduced serum level of IGF-1 by 90%. These effects were associated with reduction in daily food intake, body weight gain and gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was without significant effect on food intake, body weight gain or growth of gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was not affected by ghrelin administration in rats with removed pituitary.


CONCLUSIONS
Administration of ghrelin stimulates gastric and duodenal growth in young mature rats with intact pituitary, but inhibits expression of mRNA for pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an essential role in growth-promoting effects of ghrelin in the stomach and duodenum.
Warzecha
Z
Z
Department of Physiology, Jagiellonian University Medical College, Krakow, Poland. mpdembin@cyf-kr.edu.pl
Dembiński
A
A
Ceranowicz
P
P
Dembiński
M
M
Cieszkowski
J
J
Konturek
S J
SJ
Polus
A
A
Pawlik
W W
WW
Kuwahara
A
A
Kato
I
I
Konturek
P C
PC
D000704:Analysis of Variance; D000818:Animals; D004386:Duodenum / Q000187:drug effects / Q000254:growth & development*; D004765:Enteropeptidase / Q000235:genetics / Q000378:metabolism*; D005753:Gastric Mucosa / Q000254:growth & development / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010434:Pepsin A / Q000378:metabolism; D020116:Pepsinogen A / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000254:growth & development*; D015430:Weight Gain
D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D020116:Pepsinogen A; D013006:Growth Hormone; D004765:Enteropeptidase; D010434:Pepsin A