Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats

Obes Res. 2002 Oct;10(10):991-9. doi: 10.1038/oby.2002.135.


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.

Research methods and procedures: 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.

Discussion: 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.

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / physiology*
  • Adrenalectomy
  • Animals
  • Body Weight / drug effects
  • Body Weight / physiology*
  • Eating / drug effects
  • Eating / physiology
  • Ghrelin
  • Growth Hormone / metabolism
  • Growth Hormone / pharmacology
  • Hypophysectomy
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiology*
  • Insulin-Like Growth Factor I / pharmacology
  • Male
  • Oligopeptides / pharmacology
  • Peptide Hormones / blood
  • Peptide Hormones / metabolism*
  • Peptide Hormones / pharmacology*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Thyroidectomy


  • Ghrelin
  • Oligopeptides
  • Peptide Hormones
  • growth hormone releasing hexapeptide
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • growth hormone-releasing peptide-2