Modulation of hypothalamic hypocretin/orexin mRNA expression by glucocorticoids

https://doi.org/10.1016/S0006-291X(02)00848-3Get rights and content

Abstract

The orexins are peptides which were recently isolated from the rat hypothlamus. They play a role in energy homeostasis and regulation of feeding as well as in other functions such as the sleep–wake cycle. The involvement of glucocorticoids in stress processes as well as in body weight regulation is well known. In the present paper, we investigated the role of glucocorticoids on hypocretin (Hcrt)/orexin (OX) pathway in Sprague–Dawley rats. We confirmed by in situ hybridization that prepro-Hcrt/OX mRNA expression is restricted to the lateral hypothalamus area with extension to the perifornical nucleus and the posterior hypothalamic area. Lateral hypothalamic prepro-Hcrt/OX mRNA expression was decreased by 50% after adrenalectomy (99.8±5.0 vs 49.2±4.4 nCi/g, p<0.01). Peripheral glucocorticoid treatment (dexamethasone) restored its expression to normal levels (105.4±6.1 nCi/g). The present data provide direct evidence that Hcrt/OX expression in the lateral hypothalamus is modulated by the glucocorticoids status. As the Hcrt/Ox system is closely interactive with the corticotropin-releasing hormone and neuropeptide Y systems, we propose that hypocretin/orexins peptides constitute a very sensitive key relay for mediating both stress and feeding behavior.

Section snippets

Materials and methods

Sham and bilaterally adrenalectomized (ADX) male Sprague–Dawley rats (body weight 250 g, IFFA CREDO, France) were individually housed in plastic cages with a stainless steel cover in a temperature-controlled room(22±2C) on a 12:12 h light/dark cycle (light on at 06h00). They were allowed ad libitum access to tap water supplemented with 9 g/L NaCl and standard rat laboratory chow diet. Three experimental groups were made (n=8 per group), a sham-operated control group treated with vehicle, an

Results

Fig. 1 shows the central distribution of prepro-Hcrt/OX mRNA using in situ hybridization in rat brain coronal section. In control rat, a strong hybridization signal was observed in the lateral hypothalamus with extension into the perifornical nucleus and the posterior hypothalamic area. In ADX rats, the signal persisted in the lateral hypothalamus, but less intense, with fewer hybridization signals in the perifornical nucleus and the posterior hypothalamic area. Almost all hybridization signals

Discussion

In the present report, we investigated the regulation of Hcrt/OX pathway by glucocorticoids by measuring Hcrt/OX brain expression in the presence or absence of corticosterone. Firstly, we confirmed that prepro-Hcrt/OX mRNA expression is restricted to the lateral hypothalamus area with extension to the perifornical nucleus and the posterior hypothalamic area [1], [2]. This pattern of expression is consistent with a role of Hcrt/OX peptides in the control of food intake [3], [4], [5], [6] and

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