Differential Effects of Adrenalectomy on Melanin-Concentrating Hormone and Orexin A

Mar 27, 2004Endocrinology

Different effects of removing the adrenal glands on two brain chemicals that regulate energy and sleep

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Abstract

Adrenalectomy (ADX) significantly reduces sensitivity to the orexigenic action of third ventricular melanin-concentrating hormone (MCH) in rats.

Glucocorticoids are associated with promoting positive energy balance by altering sensitivity to hypothalamic peptides.
ADX reduces food intake and body weight in rodents, preventing excessive weight gain in obesity models.
After ADX, rats show decreased sensitivity to the appetite-increasing effects of MCH, while responses to orexin A remain unchanged.
Replacement of corticosterone in ADX rats reverses the decreased sensitivity to MCH.
ADX leads to reduced gene expression of MCH and orexin in the hypothalamus, which is not restored by glucocorticoid replacement.

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Removal of glucocorticoids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Glucocorticoids play a key role to promote positive energy balance in normal and pathological conditions, at least in part, by altering the sensitivity to hypothalamic peptides. The hyperphagia after central neuropeptide Y administration, for example, is attenuated by ADX, and there is evidence that glucocorticoids influence both MCH and orexin A activity. In the present study, feeding responses to third ventricular MCH and orexin A were measured in rats after bilateral ADX or sham surgery. ADX rats were significantly less sensitive to the orexigenic action of third ventricular MCH, whereas orexin A-induced hyperphagia was unaffected. Replacement of corticosterone in the drinking water of ADX rats reversed the effects of ADX on MCH sensitivity. Although we found significant populations of glucocorticoid receptors in the lateral hypothalamus, none were colocalized with either MCH or orexin A-containing cell bodies. Furthermore, whereas ADX significantly reduced hypothalamic MCH and orexin gene expression, this could not be restored by glucocorticoids in the drinking water. Collectively, the present data suggest that glucocorticoids may promote food intake in part by potentiating the orexigenic actions of MCH without affecting the actions of orexin A and that glucocorticoids act indirectly to influence the effects of MCH on food intake.

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Differential Effects of Adrenalectomy on Melanin-Concentrating Hormone and Orexin A

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