Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats.
OBJECTIVE
The novel gastric hormone ghrelin has recently been identified as an important modulator of energy homeostasis. Leptin-responsive hypothalamic neuropeptide Y/Agouti-related protein neurons are believed to mediate afferent ghrelin signals. Little is known, however, about ghrelin-induced efferent signals. We therefore investigated if hypothalamic-pituitary axes have a role in transferring ghrelin-induced changes of energy balance to the periphery.


METHODS
We subcutaneously injected hypophysectomized, as well as adrenalectomized, thyroidectomized, and sham-operated control rats with GH secretagogues [ghrelin, growth hormone (GH)-releasing peptide] for 1 week. Body weight, food intake, and body composition (chemical carcass analysis) were analyzed and compared with vehicle-treated controls. In addition, we quantified circulating levels of endogenous ghrelin in hypophysectomized and GH-treated normal rats.


RESULTS
GH-secretagogue treatment of sham-operated control rats dose-proportionally increased food intake, body weight, and fat mass compared with vehicle-injected controls (p < 0.01). These effects, however, were not observed in ghrelin-treated hypophysectomized, thyroidectomized, or adrenalectomized rats, indicating an essential role for the pituitary axis in ghrelin-induced adiposity. Circulating levels of endogenous ghrelin were reduced by administration of GH in normal rats and were about 3-fold higher in hypophysectomized rats (n = 20, p = 0.001), suggesting a regulatory feedback loop involving the stomach and the pituitary to regulate gastric ghrelin secretion.


CONCLUSIONS
According to these results, the endocrine pituitary is mediating ghrelin-induced changes toward a positive energy balance and is involved in the regulation of ghrelin secretion through a gastro-hypophyseal feedback loop.
Tschöp
Matthias
M
German Institute of Human Nutrition, Bergh.-Rehbrücke, Germany. tschoep@mail.dife.de
Flora
David B
DB
Mayer
John P
JP
Heiman
Mark L
ML
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy
D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C091874:growth hormone-releasing peptide-2