Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity.
Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake. GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary. Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach. Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown. We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. Tg rats had lower body weight and less adipose tissue than did control rats. Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats. GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats. These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity.
Shuto
Yujin
Y
Department of Medicine, Nippon Medical School, Tokyo, Japan. shuto@nms.ac.jp
Shibasaki
Tamotsu
T
Otagiri
Asuka
A
Kuriyama
Hideki
H
Ohata
Hisayuki
H
Tamura
Hideki
H
Kamegai
Jun
J
Sugihara
Hitoshi
H
Oikawa
Shinichi
S
Wakabayashi
Ichiji
I
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008024:Ligands; D008297:Male; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones; D010455:Peptides / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D012737:Sex Factors; D013997:Time Factors
D054439:Ghrelin; D008024:Ligands; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013006:Growth Hormone; D004247:DNA; C091874:growth hormone-releasing peptide-2