Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats.
Tschöp. Matthias M; Flora. David B DB; Mayer. John P JP; Heiman. Mark L ML
Key Findings
- Ghrelin/GHRP‑2 increases food intake, body weight, and fat mass in normal rats.
- Removing the pituitary (hypophysectomy) blocks the weight‑gain effect of ghrelin, indicating the pituitary mediates ghrelin‑induced adiposity.
- Administering GH lowers circulating ghrelin, while pituitary‑less rats have three‑fold higher ghrelin, suggesting a feedback loop between the stomach and pituitary.
Practical Outcomes
- For biohackers using GHRP‑2, expect increased appetite and potential fat gain because the pituitary is intact in humans. Monitoring calorie intake or pairing GHRP‑2 with strategies that limit excess calories may be necessary. The study also hints that high GH levels can suppress natural ghrelin, which could influence timing or dosing decisions.
Summary
In rats, giving ghrelin or GHRP‑2 makes normal animals eat more, gain weight and store fat, but if the pituitary gland is removed those effects disappear. This shows that the pituitary is needed for ghrelin‑driven weight gain, and that high GH levels can suppress the body’s own ghrelin production.
Abstract
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. 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. 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. 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.
Study Information
pubmed
2002
10.1038/oby.2002.135