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

M Tschöp, DB Flora, JP Mayer, ML Heiman - Obesity Research, 2002 - Wiley Online Library
Obesity Research, 2002Wiley Online Library
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 …
Abstract
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.
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